Vai ai contenuti. | Spostati sulla navigazione | Spostati sulla ricerca | Vai al menu | Contatti | Accessibilità

| Crea un account

Munari, Francesca (2009) NMR and biochemical analysis of protein-protein interactions: insights on dopamine synthesis regulation and heterochromatin formation. [Tesi di dottorato]

Full text disponibile come:

[img]
Anteprima
Documento PDF
11Mb

Abstract (inglese)

Molecular recognition between proteins plays a fundamental role in almost all biological processes. Therefore, the structural characterization of protein-protein interactions represents a fundamental tool to shed light on the molecular mechanisms of biological events. Moreover, it can elucidate the structural basis of the function for proteins without a detectable catalytic activity.
The regulation of dopamine synthesis is an example of the importance of protein-protein interactions in the modulation of a biological function.
L-Dopamine, one of the catecholaminergic neurotransmitters, has many functions in the brain, including regulation of behavior and cognition, motor activity, and sleep.
The enzyme responsible for the biosynthesis of its precursor L-DOPA, named Tyrosine Hydroxylase, is therefore tightly regulated by different mechanisms. One of the most important is the interaction with protein modulators. 14-3-3 proteins bind to the N-terminal regulatory domain of Tyrosine Hydroxylase, leading to the stabilization of the active conformer. Several published data suggest that also alpha-synuclein, a natively unfolded protein linked to the pathogenesis of Parkinson Disease, could play a role in dopamine synthesis, through the inhibition of Tyrosine Hydroxylase. Interestingly, experimental evidence exists also for the interaction between 14-3-3 protein and alpha-synuclein: the binding has been supposed to have functional significance in the network regulation of dopamine synthesis.
The first part of this research is focused on the characterization of the interactions among these three key protein modulators of dopamine biosynthesis using a combined biochemical and spectroscopic approach.
The work can be devided into different levels. Molecular biology, biochemical and spectroscopic methods were used to obtain and characterise each protein sample separately. Subsequently, we analysed the interaction between each pair of protein partners using both biochemical and biophysical tools, in particular NMR spectroscopy.
Electrophoretic and chromatographic results revealed that alpha-synuclein and 14-3-3 proteins fail to form a stable complex in solution, while NMR experiments suggest a transient interaction involving only the first N-terminal residues of monomeric alpha-synuclein. However, a strong indication of interaction comes from aggregation experiments followed by fluorescence polarization, where 14-3-3 proteins were demonstrated to slow down the alpha-synuclein aggregation rate. Taken together, these results suggest that 14-3-3 proteins may bind to the alpha-synuclein oligomeric species, thus opening a possible chaperon function of 14-3-3 proteins to prevent alpha-synuclein aggregation and fibrillation.
On the other hand, both enzymatic and NMR experiments indicated that alha-synuclein does not inhibit Tyrosine Hydroxylase and there is no direct interaction between the two proteins in the experimental conditions tested.
Finally, we verified, using biochemical tools, the formation of a complex with high affinity between 14-3-3 proteins and Tyrosine Hydroxylase phosphorylated in Serine 19, and carried out preliminary crystallization screenings of the complex.
Moreover, this research includes the NMR structural investigation of a second example of protein-protein interaction, involved in a different biological function. We analysed the molecular recognition mechanism between Heterochromatin protein 1 (Hp1beta) and a twenty-one residues peptide that mimics the histone 3 N-terminal tail of the nucleosome. The Hp1beta/histone 3 interaction leads to the packaging of the DNA in tertiary and quaternary structures, altogether named heterochromatin. As heterochromatin prevents access of the transcriptional machinery to the DNA, its formation represents a regulatory mechanism to inhibit gene expression in specific regions of the genome.
As necessary premise to study this interaction by NMR, we assigned, using heteronuclear 3D experiments, the 1H,15N and 13C backbone chemical shifts of Hp1beta protein. At present, we completed the assignment of the resonances from the domain that mediates the interaction with histone 3, called chromo-domain. The assignment of the signals from the other two parts of the molecule, named hinge region and chromo-shadow domain, is in progress. We then characterised the tumbling of the different parts of Hp1beta protein by cross-correlation experiments. Residual dipolar couplings were used to compare the structure of the chromo-domain domain in the full-length protein with that published for the domain produced as deleted mutant.
[1H,15N] HSQC experiments were obtained titrating Hp1beta with the histone 3 derived peptide. The results of the chemical shift perturbation analysis allowed us to map the residues of Hp1beta protein that are responsible for the interaction with the histone 3 N-terminal tail.

Abstract (italiano)

Il riconoscimento molecolare tra proteine riveste un ruolo fondamentale nella gran parte dei processi biologici. Pertanto, la caratterizzazione strutturale delle interazioni proteina-proteina rappresenta una chiave di lettura fondamentale per far luce sui meccanismi molecolari alla base dei processi biologici. Inoltre tale caratterizzazione può chiarire le basi strutturali della funzione di quelle proteine che mancano di attività catalitica rilevabile.
La regolazione della sintesi di dopamina è un esempio dell'importanza delle interazioni proteina-proteina nella modulazione delle funzioni biologiche. La dopamina, uno dei neurotrasmettitori catecolamminergici, regola molte funzioni del sistema nervoso, tra cui quelle legate al comportamento ed ai processi cognitivi, all’attività motoria e al sonno. L'enzima responsabile della sintesi del suo precursore L-DOPA, è la Tirosina Idrossilasi. Data l’importanza della sua attività catalitica, l’enzima è finemente regolato da molteplici meccanismi. Uno dei più importanti è basato sull’interazione con modulatori proteici.
Le proteine 14-3-3 legano il dominio regolatore ammino-terminale della Tirosina Idrossilasi, stabilizzandone la conformazione cataliticamente attiva. Diversi dati pubblicati in letteratura sostengono che anche l’alfa-sinucleina, una proteina “natively unfolded” correlata all’insorgenza del morbo di Parkinson, potrebbe avere una funzione nella sintesi della dopamina, attraverso l'inibizione della Tirosina Idrossilasi. Di particolare interesse sono le evidenze sperimentali che dimostrano l'interazione tra alfa-sinucleina e proteine 14-3-3, che potrebbe giocare un ruolo importante nella complessa rete di regolazione della sintesi della dopamina.
La prima parte di questa ricerca è focalizzata sulla caratterizzazione delle interazioni fra i tre modulatori proteici della sintesi della dopamina, attraverso l’utilizzo combinato di tecniche biochimiche e spettroscopiche.
Il lavoro si articola in più livelli. Metodi di biologia molecolare, biochimica e spettroscopia sono stati impiegati per produrre e caratterizzare i campioni di proteine per i successivi studi. Abbiamo poi analizzato l'interazione di ciascuna coppia di proteine, utilizzando sia tecniche di biochimica e di biofisica, in particolare spettroscopia di risonanza magnetica nucleare (NMR). Dai risultati elettroforetici e cromatografici è emerso che alfa-sinucleina e proteine 14-3-3 non formano un complesso stabile in soluzione, mentre esperimenti NMR suggeriscono che vi sia una interazione debole che coinvolge solo i primi residui della regione ammino-terminale dell' alfa-sinucleina. Tuttavia, esperimenti di aggregazione seguendo il segnale di polarizzazione di fluorescenza, portano ad una forte indicazione dell’interazione tra le due proteine, dimostrando che le proteine 14-3-3 sono in grado di rallentare la velocità di aggregazione dell’alfa-sinucleina. Complessivamente i risultati suggeriscono che le proteine 14-3-3 potrebbero legarsi alle specie oligomeriche dell' alfa-sinucleina, aprendo quindi la strada ad una possibile funzione di “chaperon” nell’ inibizione del processo di aggregazione e fibrillazione dell’ alfa-sinucleina.
Invece, sia gli studi di attività enzimatica che NMR, indicano che l’ alfa-sinucleina non è un inibitore della Tirosina Idrossilasi, e che non c’è interazione diretta tra le due proteine nelle condizioni sperimentali utilizzate.
Infine, mediante tecniche biochimiche, abbiamo verificato che le proteine 14-3-3 e Tirosina Idrossilasi fosforilata sulla serina 19, formano un complesso ad alta affinità. Abbiamo quindi purificato il complesso su larga scala, ed effettuato lo screening preliminare di cristallizzazione.
La seconda parte del lavoro di ricerca si occupa dell’ indagine strutturale, mediante NMR, di un secondo esempio di interazione proteina-proteina che è alla base di una differente funzione biologica. Abbiamo analizzato il meccanismo di riconoscimento molecolare tra “Heterochromatin protein 1” (Hp1beta) ed un peptide di ventuno residui che mima la regione ammino-terminale della proteina istonica, appartenente al complesso proteico nucleosoma. L’interazione tra Hp1beta e l’istone III porta all’impacchettamento del DNA in strutture terziarie e quaternarie, definite complessivamente eterocromatina. Dal momento che l’eterocromatina impedisce l'accesso dell’apparato di trascrizione al DNA, la sua formazione rappresenta un meccanismo di regolazione per inibire l'espressione genica in specifiche regioni del genoma.
Il requisito fondamentale per studiare questa interazione mediante NMR, è l’assegnazione, utilizzando esperimenti tridimensionali eteronucleari, delle risonanze di 1H, 15N e 13C della catena polipeptidica della proteina Hp1beta. Ad oggi abbiamo completato l’assegnazione dei segnali relativi al dominio che media l’interazione con la proteina istonica III, definito “chromo-domain”. L'assegnazione dei segnali relativi alle altre due regioni della molecola, definiti “hinge-region” e “chromo-shadow domain”, è tuttora in corso. Abbiamo poi caratterizzato le proprietà di “tumbling” delle diverse regioni della proteina Hp1beta, mediante particolari esperimenti di rilassamento di magnetizzazione, definiti di “cross-correlation”. I valori di “residual dipolar coupling” sono stati utilizzati per confrontare la struttura del “chromo-domain” compreso nella proteina intera, con la struttura pubblicata dello stesso dominio prodotto come mutante di delezione.
Tramite esperimenti di titolazione per risonanza magnetica nucleare abbiamo infine individuato i residui amminoacidici della proteina Hp1beta che sono coinvolti nel riconoscimento molecolare del peptide. I risultati dell’analisi delle differenze nei valori di “chemical shift”, ha consentito di mappare le regioni della proteina Hp1beta che sono coinvolte nell'interazione con la parte ammino-terminale dell'istone III.

Statistiche Download - Aggiungi a RefWorks
Tipo di EPrint:Tesi di dottorato
Relatore:Mammi, Stefano
Dottorato (corsi e scuole):Ciclo 21 > Scuole per il 21simo ciclo > SCIENZE MOLECOLARI > SCIENZE CHIMICHE
Data di deposito della tesi:01 Febbraio 2009
Anno di Pubblicazione:02 Febbraio 2009
Parole chiave (italiano / inglese):NMR, synuclein, 14-3-3, Tyrosine Hydroxylase, Hp1, protein interactions, molecular recognition
Settori scientifico-disciplinari MIUR:Area 03 - Scienze chimiche > CHIM/02 Chimica fisica
Struttura di riferimento:Dipartimenti > Dipartimento di Scienze Chimiche
Codice ID:1897
Depositato il:01 Feb 2009
Simple Metadata
Full Metadata
EndNote Format

Bibliografia

I riferimenti della bibliografia possono essere cercati con Cerca la citazione di AIRE, copiando il titolo dell'articolo (o del libro) e la rivista (se presente) nei campi appositi di "Cerca la Citazione di AIRE".
Le url contenute in alcuni riferimenti sono raggiungibili cliccando sul link alla fine della citazione (Vai!) e tramite Google (Ricerca con Google). Il risultato dipende dalla formattazione della citazione.

Abeliovich, A., Schmitz, Y., Farinas, I., Choi-Lundberg, D., Ho, W. H., Castillo, P. E., Shinsky, N., Verdugo, J. M., Armanini, M., Ryan, A., Hynes, M., Phillips, H., Sulzer, D., and Rosenthal, A. Neuron 2000; 25, 239–252. Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Cerca con Google

Aitken A. Semin Cancer Biol. 2006 Jun;16(3):162-72. 14-3-3 proteins: a historic overview. Cerca con Google

Albert KA, Helmer-Matyjek E, Nairn AC, Müller TH, Haycock JW, Greene LA, Goldstein M, Greengard P. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7713-7. Calcium/phospholipid-dependent protein kinase (protein kinase C) phosphorylates and activates tyrosine hydroxylase. Cerca con Google

Almås B, Le Bourdelles B, Flatmark T, Mallet J, Haavik J.Eur J Biochem. 1992 Oct 1;209(1):249-55. Cerca con Google

Regulation of recombinant human tyrosine hydroxylase isozymes by catecholamine binding and phosphorylation. Structure/activity studies and mechanistic implications. Cerca con Google

Alterio J, Ravassard P, Haavik J, Le Caer JP, Biguet NF, Waksman G, Mallet J. J Biol Chem. 1998 Apr 24;273(17):10196-201. Human tyrosine hydroxylase isoforms. Inhibition by excess tetrahydropterin and unusual behavior of isoform 3 after camp-dependent protein kinase phosphorylation. Cerca con Google

Arents G, Burlingame RW, Wang BC, Love WE, Moudrianakis EN. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10148-52. The nucleosomal core histone octamer at 3.1 A resolution: a tripartite protein assembly and a left-handed superhelix. Cerca con Google

Ball LJ, Murzina NV, Broadhurst RW, Raine AR, Archer SJ, Stott FJ, Murzin AG, Singh PB, Domaille PJ, Laue ED. EMBO J. 1997 May 1;16(9):2473-81. Structure of the chromatin binding (chromo) domain from mouse modifier protein 1. Cerca con Google

Banik U, Wang GA, Wagner PD, Kaufman S. J Biol Chem. 1997 Oct 17;272(42):26219-25. Interaction of phosphorylated tryptophan hydroxylase with 14-3-3 proteins. Cerca con Google

Barnham KJ, Masters CL, Bush AI. Nat Rev Drug Discov. 2004 Mar;3(3):205-14. Neurodegenerative diseases and oxidative stress. Cerca con Google

Bassan A, Blomberg MR, Siegbahn PE. Chemistry. 2003 Jan 3;9(1):106-15. Mechanism of dioxygen cleavage in tetrahydrobiopterin-dependent amino acid hydroxylases. Cerca con Google

Bax A, Grishaev A.. Curr Opin Struct Biol. 2005 Oct;15(5):563-70. Review. Weak alignment NMR: a hawk-eyed view of biomolecular structure. Cerca con Google

Berg D, Holzmann C, Riess O. Nat Rev Neurosci. 2003 Sep;4(9):752-62. 14-3-3 proteins in the nervous system. Cerca con Google

Berg, D., Riess, O. & Bornemann, A. Ann. Neurol. 2003; 53, 135. Specification of 14-3–3 proteins in Lewy bodies. Cerca con Google

Bertoncini, C. W., Jung, Y. S., Fernandez, C. O., Hoyer, W., Griesinger, C., Jovin, T. M., and Zweckstetter, M. Proc. Natl. Acad. Sci. U. S. A. 2005; 102, 1430–1435. Release of long-range tertiary interactions potentiates aggregation of natively unstructured alpha-synuclein. Cerca con Google

Bisaglia M, Mammi S, Bubacco L. FASEB J. 2009 Feb; 23(2): 329-340. Structural insights on physiological functions and pathological effects of {alpha}-synuclein. Cerca con Google

Bisaglia M, Tessari I, Pinato L, Bellanda M, Giraudo S, Fasano M, Bergantino E, Bubacco L, Mammi S. Biochemistry. 2005 Jan 11;44(1):329-39. A topological model of the interaction between alpha-synuclein and sodium dodecyl sulfate micelles. Cerca con Google

Blackledge M., Prog Nucl Magn Reson Spectrosc. 2005; 46 23–61. Recent progress in the study of biomolecular structure and dynamics in solution from residual dipolar couplings, Bodles, A. M., Guthrie, D. J., Greer, B., and Irvine, G. B. J. Neurochem. 2001; 78, 384–395 Identification of the region of non-Abeta component (NAC) of Alzheimer’s disease amyloid responsible for its aggregation and toxicity. Cerca con Google

Bortolus, M., Tombolato, F., Tessari, I., Bisaglia, M., Mammi, S., Bubacco, L., Ferrarini, A., and Maniero, A. L. J. Am. Chem. Soc. 2008; 130, 6690–6691. Broken helix in vesicle and micelle-bound alpha-synuclein: insights from site-directed spin labeling-EPR experiments and MD simulations. Cerca con Google

Bottomley MJ. EMBO Rep. 2004 May;5(5):464-9. Structures of protein domains that create or recognize histone modifications. Cerca con Google

Bradford, M. M. Anal. Biochem. 1976 72:248-254. A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding. Cerca con Google

Braselmann S, McCormick F. EMBO J. 1995 Oct 2;14(19):4839-48. Bcr and Raf form a complex in vivo via 14-3-3 proteins. Cerca con Google

Brasher SV, Smith BO, Fogh RH, Nietlispach D, Thiru A, Nielsen PR, Broadhurst RW, Ball LJ, Murzina NV, Laue ED. EMBO J. 2000 Apr 3;19(7):1587-97. The structure of mouse HP1 suggests a unique mode of single peptide recognition by the shadow chromo domain dimer. Cerca con Google

Bussell, R., Jr., and Eliezer, D. J. Biol. Chem. 2001; 276, 45996–46003. Residual structure and dynamics in Parkinson’s disease-associated mutants of alphasynuclein. Cerca con Google

Chandra, S., Chen, X., Rizo, J., Jahn, R., Sudhof, T. J. Biol. Chem.2003; 278, 15313–15318. A broken alpha -helix in folded alpha -Synuclein. Cerca con Google

Chartier-Harlin, M. C., Kachergus, J., Roumier, C., Mouroux, V., Douay, X., Lincoln, S., et al. Lancet 2004; 364 1167–1169 Cerca con Google

Chaudhri M, Scarabel M, Aitken A. Biochem Biophys Res Comm. 2003;300:679–85. Mammalian and yeast 14-3-3 isoforms form distinct patterns of dimers in vivo. Chen, M., Margittai, M., Chen, J., and Langen, R. J. Biol. Chem. 2007; 282, 24970–24979. Investigation of alpha-synuclein fibril structure by site-directed spin labeling. Cheung P, Allis CD, Sassone-Corsi P. Cell. 2000 Oct 13;103(2):263-71. Review. Signaling to chromatin through histone modifications. Cerca con Google

Cheung E, Schwabish MA, Kraus WL. EMBO J. 2003 Feb 3;22(3):600-11. Chromatin exposes intrinsic differences in the transcriptional activities of estrogen receptors alpha and beta. Cerca con Google

Cho MK, Kim HY, Bernado P, Fernandez CO, Blackledge M, Zweckstetter M. J Am Chem Soc. 2007 Mar 21;129(11):3032-3. Amino acid bulkiness defines the local conformations and dynamics of natively unfolded Cerca con Google

alpha-synuclein and tau. Clayton, D. F., and George, J. M. Trends Neurosci. 1998; 21, 249–254 The synucleins: a family of proteins involved in synaptic function, plasticity, neurodegeneration and disease. Cerca con Google

Conway, K. A., Lee, S. J., Rochet, J. C., Ding, T. T., Williamson, R. E., and Lansbury, P. T., Jr. Proc. Natl. Acad. Sci.U. S. A. 2000; 97, 571–576. Cerca con Google

Acceleration of oligomerization, not fibrillization, is a shared property of both alpha synuclein mutations linked to early-onset Parkinson’s disease: implications for pathogenesis and therapy. Cerca con Google

Conway, K. A., Rochet, J. C., Bieganski, R. M., and Lansbury, P. T., Jr. Science 2001; 294, 1346–1349. Cerca con Google

Kinetic stabilization of the alpha-synuclein protofibril by a dopamine-alpha-synuclein adduct. Cerca con Google

Cornilescu, G., Marquardt, J.L., Ottiger, M. & Bax, A. J. Am. Chem. Soc. 1998; 120, 6836– 6837. Cerca con Google

Validation of protein structure from anisotropic carbonyl chemical shifts in a dilute liquid crystalline phase. Cerca con Google

Davidson, W. S., Jonas, A., Clayton, D. F., and George, J. M. J. Biol. Chem.1998; 273,9443–9449. Cerca con Google

Stabilization of alpha-synuclein secondary structure upon binding to synthetic membranes. Delaglio F, Grzesiek S, Vuister GW, Zhu G, Pfeifer J, Bax A. J Biomol NMR. 1995 Nov;6(3):277-93. Cerca con Google

NMRPipe: a multidimensional spectral processing system based on UNIX pipes. Dedmon, M. M., Lindorff-Larsen, K., Christodoulou, J., Vendruscolo, M., and Dobson, C. M. J. Am. Chem. Soc. 2005; 127, 476–477. Cerca con Google

Mapping long-range interactions in alpha-synuclein using spin-label NMR and ensemble molecular dynamics simulations. Cerca con Google

Dev KK, Hofele K, Barbieri S, Buchman VL, van der Putten H. Neuropharmacology. 2003 Jul;45(1):14-44. Review. Part II: alpha-synuclein and its molecular pathophysiological role in neurodegenerative disease. Cerca con Google

Dobson CM. Nature. 2003 Dec 18;426(6968):884-90. Review. Protein folding and misfolding. Cerca con Google

Drescher, M., Veldhuis, G., van Rooijen, B. D., Milikisyants, S., Subramaniam, V., and Huber, M. J. Am. Chem. Soc. 2008; 130, 7796–7797. Cerca con Google

Antiparallel arrangement of the helices of vesicle-bound alpha-synuclein. Du X, Fox JE, Pei S. J Biol Chem. 1996 Mar 29;271(13):7362-7. Cerca con Google

Identification of a binding sequence for the 14-3-3 protein within the cytoplasmic domain of the adhesion receptor, platelet glycoprotein Ib alpha. Cerca con Google

Dyson HJ, Wright PE. Adv Protein Chem. 2002;62:311-40. Review. Insights into the structure and dynamics of unfolded proteins from nuclear magnetic resonance. Cerca con Google

Dunkley PR, Bobrovskaya L, Graham ME, von Nagy-Felsobuki EI, Dickson PW. J Neurochem. 2004 Dec;91(5):1025-43. Cerca con Google

Tyrosine hydroxylase phosphorylation: regulation and consequences. Eissenberg JC, Elgin SC. Curr Opin Genet Dev. 2000 Apr;10(2):204-10. Cerca con Google

The HP1 protein family: getting a grip on chromatin. Eliezer, D., Kutluay, E., Bussell, R., Jr., and Browne, G. J. Mol. Biol. 2001; 307, 1061–1073. Cerca con Google

Conformational properties of alpha-synuclein in its free and lipid-associated states. Erlandsen H, Fusetti F, Martinez A, Hough E, Flatmark T, Stevens RC. Nat Struct Biol. 1997 Dec;4(12):995-1000. Review. Cerca con Google

Crystal structure of the catalytic domain of human phenylalanine hydroxylase reveals the structural basis for phenylketonuria. Cerca con Google

Farrer, M., and Destee, A. (2004) Alpha-synuclein locus duplication as a cause of familial Parkinson’s disease. Cerca con Google

Fernández CO, Hoyer W, Zweckstetter M, Jares-Erijman EA, Subramaniam V, Griesinger C, Jovin TM. EMBO J. 2004 May 19;23(10):2039-46. Cerca con Google

NMR of alpha-synuclein-polyamine complexes elucidates the mechanism and kinetics of induced aggregation. Cerca con Google

Fernández C, Wider G. Curr Opin Struct Biol. 2003 Oct;13(5):570-80. Review. TROSY in NMR studies of the structure and function of large biological macromolecules. Cerca con Google

Fink, A. L. Acc. Chem. Res. 2006; 39, 628–634. The aggregation and fibrillation of alphasynuclein. Cerca con Google

Fischer, M.W.F., Losonczi, J.A., Weaver, J.L. & Prestegard, J.H.1999; Biochemistry 38, 9013–9022. Domain orientation and dynamics in multidomain proteins from residual dipolar couplings. Cerca con Google

Fitzpatrick PF. Biochemistry. 1991 Jul 2;30(26):6386-91. Studies of the rate-limiting step in the tyrosine hydroxylase reaction: alternate substrates, solvent isotope effects, and transition-state analogues. Cerca con Google

Fitzpatrick PF. Annu Rev Biochem. 1999;68:355-81. Review. Tetrahydropterin-dependent amino acid hydroxylases. Cerca con Google

Fitzpatrick PF. Adv Enzymol Relat Areas Mol Biol. 2000;74:235-94. Review. The aromatic amino acid hydroxylases. Cerca con Google

Fitzpatrick PF. Biochemistry. 2003 Dec 9;42(48):14083-91. Review. Mechanism of aromatic amino acid hydroxylation. Cerca con Google

Fountoulakis, M., Cairns, N. & Lubec, G. J. Neural. Transm. Suppl. 1999; 57, 323–335. Increased levels of 14-3-3γ and ε proteins in brain of patients with Alzheimer’s disease and Down syndrome. Cerca con Google

Fu H, Subramanian RR, Masters SC. Annu Rev Pharmacol Toxicol. 2000;40:617-47. 14-3-3 proteins: structure, function, and regulation. Cerca con Google

Fusetti F, Erlandsen H, Flatmark T, Stevens RC. J Biol Chem. 1998 Jul 3;273(27):16962-7. Structure of tetrameric human phenylalanine hydroxylase and its implications for phenylketonuria. Cerca con Google

Gardino AK, Smerdon SJ, Yaffe MB. Semin Cancer Biol. 2006 Jun;16(3):173-82. Structural determinants of 14-3-3 binding specificities and regulation of subcellular localization of 14-3-3-ligand complexes: a comparison of the X-ray crystal structures of all human 14-3-3 isoforms. Cerca con Google

Giasson, B. I., Murray, I. V., Trojanowski, J. Q., and Lee, V. M. J. Biol. Chem.2001; 276, 2380–2386. Cerca con Google

A hydrophobic stretch of 12 amino acid residues in the middle of alpha-synuclein is essential for filament assembly. Cerca con Google

Goodwill KE, Sabatier C, Marks C, Raag R, Fitzpatrick PF, Stevens RC. Nat Struct Biol. 1997 Jul;4(7):578-85. Cerca con Google

Crystal structure of tyrosine hydroxylase at 2.3 Å and its implications for inherited neurodegenerative diseases. Cerca con Google

Goodwill KE, Sabatier C, Stevens RC. Biochemistry. 1998 Sep 29;37(39):13437-45. Crystal structure of tyrosine hydroxylase with bound cofactor analogue and iron at 2.3 Å resolution: self-hydroxylation of Phe300 and the pterin-binding site. Cerca con Google

Grima B, Lamouroux A, Boni C, Julien JF, Javoy-Agid F, Mallet J. Nature. 1987 Apr 16- 22;326(6114):707-11. Cerca con Google

A single human gene encoding multiple tyrosine hydroxylases with different predicted functional characteristics. Cerca con Google

Haavik J, Almås B, Flatmark T. J Neurochem. 1997 Jan;68(1):328-32. Generation of reactive oxygen species by tyrosine hydroxylase: a possible contribution to the degeneration of dopaminergic neurons? Cerca con Google

Haavik J, Martínez A, Flatmark T. FEBS Lett. 1990 Mar 26;262(2):363-5. pH-dependent release of catecholamines from tyrosine hydroxylase and the effect of phosphorylation of Ser-40. Cerca con Google

Haycock JW. J Neurochem. 2002 Jun;81(5):947-53. Species differences in the expression of multiple tyrosine hydroxylase protein isoforms. Cerca con Google

Haycock JW. J Neurochem. 1993 Feb;60(2):493-502. Multiple forms of tyrosine hydroxylase in human neuroblastoma cells: quantitation with isoform specific antibodies. Cerca con Google

Haycock JW. J Neurochem. 1991 Jun;56(6):2139-42. Four forms of tyrosine hydroxylase are present in human adrenal medulla. Cerca con Google

Haycock JW. J Biol Chem. 1990 Jul 15;265(20):11682-91. Phosphorylation of tyrosine hydroxylase in situ at serine 8, 19, 31, and 40. Cerca con Google

Hiller S, Wasmer C, Wider G, Wüthrich K. J Am Chem Soc. 2007 Sep 5;129(35):10823-8. Sequence-specific resonance assignment of soluble nonglobular proteins by 7D APSYNMR spectroscopy. Cerca con Google

Hsich, G., Kenney, K., Gibbs, C. J., Lee, K. H. & Harrington, N. Engl. J. Med. 1996; 335, 24–30. Cerca con Google

The 14-3-3 brain protein in cerebrospinal fluid as a marker for transmissible spongiform encephalopathies. Cerca con Google

Huang C, Ren G, Zhou H, Wang CC. Protein Expr Purif. 2005 Jul;42(1):173-7. A new method for purification of recombinant human alpha-synuclein in Escherichia coli. Cerca con Google

Hufton SE, Jennings IG, Cotton RG. Biochem J. 1995 Oct 15;311 ( Pt 2):353-66. Review. Structure and function of the aromatic amino acid hydroxylases. Cerca con Google

Ichimura T, Isobe T, Okuyama T, Takahashi N, Araki K, Kuwano R, Takahashi Y. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7084-8. Cerca con Google

Molecular cloning of cDNA coding for brain-specific 14-3-3 protein, a protein kinasedependent activator of tyrosine and tryptophan hydroxylases. Cerca con Google

Ichimura T, Isobe T, Okuyama T, Yamauchi T, Fujisawa H. FEBS Lett. 1987 Jul 13;219(1):79-82. Cerca con Google

Brain 14-3-3 protein is an activator protein that activates tryptophan 5-monooxygenase and tyrosine 3-monooxygenase in the presence of Ca2+,calmodulin-dependent protein kinase II. Cerca con Google

Ichimura T, Uchiyama J, Kunihiro O, Ito M, Horigome T, Omata S, Shinkai F, Kaji H, Isobe T. J Biol Chem. 1995 Dec 1;270(48):28515-8. Cerca con Google

Identification of the site of interaction of the 14-3-3 protein with phosphorylated tryptophan hydroxylase. Cerca con Google

Itagaki C, Isobe T, Taoka M, Natsume T, Nomura N, Horigome T, Omata S, Ichinose H, Nagatsu T, Greene LA, Ichimura T. Biochemistry. 1999 Nov 23;38(47):15673-80. Stimulus-coupled interaction of tyrosine hydroxylase with 14-3-3 proteins. Cerca con Google

Jacobs SA, Taverna SD, Zhang Y, Briggs SD, Li J, Eissenberg JC, Allis CD, Khorasanizadeh S. EMBO J. 2001 Sep 17;20(18):5232-41. Cerca con Google

Specificity of the HP1 chromo domain for the methylated N-terminus of histone H3. Jakes R, Spillantini MG, Goedert M. FEBS Lett. 1994 May 23;345(1):27-32. Identification of two distinct synucleins from human brain. Cerca con Google

Jao, C. C., Der-Sarkissian, A., Chen, J., and Langen, R. Proc. Natl. Acad. Sci. U. S. A. 2004; 101, 8331–8336. Cerca con Google

Structure of membrane-bound alpha-synuclein studied by site directed spin labeling. Jenco JM, Rawlingson A, Daniels B, and Morris AJ. Biochemistry 1998; 37(14):4901–4909. Regulation of phospholipase D2: selective inhibition of mammalian phospholipase D isoenzymes by alpha- and beta-synucleins. Cerca con Google

Jones DH, Ley S, Aitken A. FEBS Lett. 1995 Jul 10;368(1):55-8. Isoforms of 14-3-3 protein can form homo- and heterodimers in vivo and in vitro: implications for function as adapter proteins. Cerca con Google

Kappock TJ, Caradonna JP. Chem Rev. 1996 Nov 7;96(7):2659-2756. Pterin-Dependent Amino Acid Hydroxylases. Cerca con Google

Kawamoto Y, Akiguchi I, Nakamura S, Honjyo Y, Shibasaki H, Budka H.. J Neuropathol Exp Neurol. 2002 Mar;61(3):245-53. 14-3-3 proteins in Lewy bodies in Parkinson disease and diffuse Lewy body disease brains. Kim, H. Y., Heise, H., Fernandez, C. O., Baldus, M., and Zweckstetter, M. Chembiochem. 2007; 8, 1671–1674. Cerca con Google

Correlation of amyloid fibril beta structure with the unfolded state of alpha-synuclein. Kim, Y. S., Laurine, E., Woods, W., and Lee, S. J. J. Mol. Biol.2006; 360, 386–397. Cerca con Google

A novel mechanism of interaction between alpha-synuclein and biological membranes. Kleppe R, Haavik J. FEBS Lett. 2004 May 7;565(1-3):155-9. Cerca con Google

Different stabilities and denaturation pathways for structurally related aromatic amino acid hydroxylases. Cerca con Google

Kleppe R, Toska K, Haavik J. J Neurochem. 2001 May;77(4):1097-107. Cerca con Google

Interaction of phosphorylated tyrosine hydroxylase with 14-3-3 proteins: evidence for a phosphoserine 40-dependent association. Cerca con Google

Kruger, R., Kuhn, W., Muller, T., Woitalla, D., Graeber, M., Kosel, S., Przuntek, H., Epplen, J. T., Schols, L., and Riess, O. Nat. Genet. 1998; 18, 106–108. Cerca con Google

Ala30Pro mutation in the gene encoding alpha synuclein in Parkinson’s disease. Kumer SC, Vrana KE. J Neurochem. 1996 Aug;67(2):443-62. Review. Intricate regulation of tyrosine hydroxylase activity and gene expression. Cerca con Google

Lashuel, H. A., Hartley, D., Petre, B. M., Walz, T., and Lansbury, P. T., Jr. Nature 2002; 418, 291. Neurodegenerative disease: amyloid pores from pathogenic mutations. Cerca con Google

Lange OF, Lakomek NA, Farès C, Schröder GF, Walter KF, Becker S, Meiler J, Grubmüller H, Griesinger C, de Groot BL. Science. 2008 Jun 13;320(5882):1471-5. Recognition dynamics up to microseconds revealed from an RDC-derived ubiquitin ensemble in solution. Cerca con Google

Le Bourdellès B, Boularand S, Boni C, Horellou P, Dumas S, Grima B, Mallet J. J Neurochem. 1988 Mar;50(3):988-91. Cerca con Google

Analysis of the 5' region of the human tyrosine hydroxylase gene: combinatorial patterns of exon splicing generate multiple regulated tyrosine hydroxylase isoforms. Cerca con Google

Lee, J. C., Langen, R., Hummel, P. A., Gray, H. B., and Winkler, J. R. Proc. Natl. Acad. Sci. U. S. A. 2004; 101, 16466–16471. Alpha-synuclein structures from fluorescence energy-transfer kinetics: implications for the role of the protein in Parkinson’s disease. Cerca con Google

Lee FJ, Liu F, Pristupa ZB, Niznik HB. FASEB J. 2001 Apr;15(6):916-26. Direct binding and functional coupling of alpha-synuclein to the dopamine transporters Cerca con Google

accelerate dopamine-induced apoptosis. Cerca con Google

Lee, J. C., Gray, H. B., and Winkler, J. R. J. Am. Chem. Soc. 2005; 127, 16388–16389. Tertiary contact formation in alpha-synuclein probed by electron transfer. Lee D, Hilty C, Wider G, Wüthrich K. J Magn Reson. 2006 Jan;178(1):72-6. Effective rotational correlation times of proteins from NMR relaxation interference. Cerca con Google

Lee, D., Lee, S.Y., Lee, E.N., Chang, C.S., Paik, S.R., Journal of Neurochemistry 2002; 82, 1007–1017. alpha-Synuclein exhibits competitive interaction between calmodulin and synthetic membranes. Cerca con Google

Levitt M.H, 2001, WILEY. Spin dynamics. Basics of Nuclear Magnetic Resonances. Cerca con Google

Lipsitz RS. and N. Tjandra Annu Rev Biophys Biomol Struct. 2004; 33. 387–413. Residual dipolar couplings in NMR structure analysis. Cerca con Google

Liu, S., Ninan, I., Antonova, I., Battaglia, F., Trinchese, F., Narasanna, A., Kolodilov, N., Dauer, W., Hawkins, R. D., and Arancio, O. EMBO J. 2004; 23, 4506–4516. alpha-Synuclein produces a long-lasting increase in neurotransmitter release. Cerca con Google

Ludecke, B.; Dworniczak, B.; Bartholome, K. Hum. Genet. 95:123-125, 1995. A point mutation in the tyrosine hydroxylase gene associated with Segawa's syndrome. Cerca con Google

Ludecke, B.; Knappskog, P. M.; Clayton, P. T.; Surtees, R. A. H.; Clelland, J. D.; Heales, S. J. R.; Brand, M. P.; Bartholome, K.; Flatmark, T. Hum. Molec. Genet. 5: 1023-1028, 1996. Recessively inherited L-DOPA-responsive parkinsonism in infancy caused by a point mutation (L205P) in the tyrosine hydroxylase gene. Cerca con Google

Luk KC, Mills IP, Trojanowski JQ, Lee VM. Biochemistry. 2008 Nov 1. Interactions between Hsp70 and the Hydrophobic Core of alpha-Synuclein Inhibit Fibril Assembly. Cerca con Google

Luk KC, Hyde EG, Trojanowski JQ, Lee VM. Biochemistry. 2007 Nov 6;46(44):12522-9. Sensitive fluorescence polarization technique for rapid screening of alpha-synuclein oligomerization/fibrillization inhibitors. Cerca con Google

Luger K, Rechsteiner TJ, Flaus AJ, Waye MM, Richmond TJ.J Mol Biol. 1997 Sep 26;272(3):301-11. Characterization of nucleosome core particles containing histone proteins made in bacteria. Cerca con Google

Maiti, N. C., Apetri, M. M., Zagorski, M. G., Carey, P. R., and Anderson, V. E. J. Am. Chem. Soc. 2004; 126, 2399–2408. Raman spectroscopic characterization of secondary structure in natively unfolded proteins: Cerca con Google

alpha-synuclein. Cerca con Google

Maroteaux, L., Campanelli, J. T., and Scheller, R. H. J. Neurosci. 1988; 8, 2804–2815. Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal. Cerca con Google

Martinez J, Moeller I, Erdjument-Bromage H, Tempst P, Lauring B. J Biol Chem. 2003 May 9;278(19):17379-87. Cerca con Google

Parkinson's disease-associated alpha-synuclein is a calmodulin substrate. McLaurin, J., Yip, C. M., St George-Hyslop, P., and Fraser, P. E. J. Biol. Chem. 2000; 275, 34328–34334. Cerca con Google

alpha-Synuclein membrane interactions and lipid specificity. Mohana-Borges, R., Goto, N.K., Kroon, G.J.A., Dyson, H.J. & Wright, P.E. J. Mol. Biol. 2004; 340, 1131–1142. Cerca con Google

Structural characterization of unfolded states of apomyoglobin using residual dipolar couplings. Cerca con Google

Moore B, Perez VJ. Physiological and biochemical aspects of nervous integration. Carlson FD, editor. Prentice-Hall; 1967; 343–59. Cerca con Google

Specific acidic proteins of the nervous system. Murray, I. V., Giasson, B. I., Quinn, S. M., Koppaka, V., Axelsen, P. H., Ischiropoulos, H., Trojanowski, J. Q., and Lee, V. M. Biochemistry 2003; 42, 8530–8540 Cerca con Google

Role of alpha-synuclein carboxy-terminus on fibril formation in vitro. Cerca con Google

Nakashima A, Mori K, Suzuki T, Kurita H, Otani M, Nagatsu T, Ota A. J Neurochem. 1999 May;72(5):2145-53. Cerca con Google

Dopamine inhibition of human tyrosine hydroxylase type 1 is controlled by the specific portion in the N-terminus of the enzyme. Cerca con Google

Nagatsu T, Levitt M, Udenfriend S. J Biol Chem. 1964 Sep;239:2910-7. Tyrosine Hydroxylase. The initial step in Norepinephrine biosynthesis. Cerca con Google

Nagatsu T. Essays Biochem. 1995;30:15-35. Review. Tyrosine hydroxylase: human isoforms, structure and regulation in physiology and pathology. Cerca con Google

Nielsen PR, Nietlispach D, Mott HR, Callaghan J, Bannister A, Kouzarides T, Murzin AG, Murzina NV, Laue ED. Nature. 2002 Mar 7;416(6876):103-7. Structure of the HP1 chromodomain bound to histone H3 methylated at lysine 9. Cerca con Google

Obsil T, Ghirlando R, Klein DC, Ganguly S, Dyda F. Cell 2001;105:257–67. Crystal structure of the 14-3-3zeta: serotonin N-acetyltransferase complex. A role for scaffolding in enzyme regulation. Cerca con Google

Obsilova V, Her. P, Vecer J, Sulc M, Teisinger J, Obsil T. J Biol Chem 2004; 279:4531–40. 14-3-3zeta C-terminal stretch changes its conformation upon ligand binding and phosphorylation at Thr232. Cerca con Google

Obsilova V, Nedbalkova E, Silhan J, Boura E, Herman P, Vecer J, Sulc M, Teisinger J, Dyda F, Obsil T. Biochemistry. 2008 Feb 12;47(6):1768-77. The 14-3-3 protein affects the conformation of the regulatory domain of human tyrosine hydroxylase. Cerca con Google

Obsilova V, Silhan J, Boura E, Teisinger J, Obsil T. Physiol Res. 2008 May 13. 14-3-3 proteins: a family of versatile molecular regulators. Cerca con Google

Ostrerova N, Petrucelli L, Farrer M, Mehta N, Choi P, Hardy J, Wolozin B. J Neurosci. 1999 Jul 15;19(14):5782-91. alpha-Synuclein shares physical and functional homology with 14-3-3 proteins. Cerca con Google

Ottiger, M., Delaglio, F., and Bax, A. J. Magn. Res. 1998; 131, 373-378. Measurement of J and Dipolar Couplings from Simplified Two-Dimensional NMR Spectra.. Cerca con Google

Panchal SC, Bhavesh NS, Hosur RV. J Biomol NMR. 2001 Jun;20(2):135-47. Improved 3D triple resonance experiments, HNN and HN(C)N, for HN and 15N sequential correlations in (13C, 15N) labeled proteins: application to unfolded proteins. Cerca con Google

Payton JE, Perrin RJ, Woods WS, George JM. J Mol Biol. 2004 Apr 2;337(4):1001-9. Structural determinants of PLD2 inhibition by alpha-synuclein. Cerca con Google

Peng X, Tehranian R, Dietrich P, Stefanis L, Perez RG. J Cell Sci. 2005 Aug 1;118:3523-30. Alpha-synuclein activation of protein phosphatase 2A reduces tyrosine hydroxylase phosphorylation in dopaminergic cells. Cerca con Google

Perez RG, Hastings TG. J Neurochem. 2004 Jun;89(6):1318-24. Review. Could a loss of alpha-synuclein function put dopaminergic neurons at risk? Cerca con Google

Perez RG, Waymire JC, Lin E, Liu JJ, Guo F, Zigmond MJ. J Neurosci. 2002 Apr 15;22(8):3090-9. A role for alpha-synuclein in the regulation of dopamine biosynthesis. Cerca con Google

Pervushin K, Riek R, Wider G, Wüthrich K. Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12366-71. Cerca con Google

Attenuated T2 relaxation by mutual cancellation of dipole-dipole coupling and chemical shift anisotropy indicates an avenue to NMR structures of very large biological macromolecules in solution. Cerca con Google

Polymeropoulos, M. H., Lavedan, C., Leroy, E., Ide, S. E. et al., Science 1997; 276, 2045– 2047 Cerca con Google

Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Cerca con Google

Powell DW, Rane MJ, Joughin BA, Kalmukova R, Hong JH, Tidor B, et al. Mol Cell Biol Cerca con Google

2003;23:5376–87. Proteomic identification of 14-3-3zeta as a mitogen-activated protein kinase-activated Cerca con Google

protein kinase 2 substrate: role in dimer formation and ligand binding. Cerca con Google

Prestegard J. H., Mayer K. L., Valafar H., Benison G. C. Methods Enzymol. 2005; 394: 175–209. Determination of Protein Backbone Structures from Residual Dipolar Couplings Cerca con Google

Quinsey NS, Luong AQ, Dickson PW.J Neurochem. 1998 Nov;71(5):2132-8. Mutational analysis of substrate inhibition in tyrosine hydroxylase. Cerca con Google

Ramsey AJ, Fitzpatrick PF. Biochemistry. 2000 Feb 1;39(4):773-8. Effects of phosphorylation on binding of catecholamines to tyrosine hydroxylase: specificity and thermodynamics. Cerca con Google

Ramsey AJ, Fitzpatrick PF. Biochemistry. 1998 Jun 23;37(25):8980-6. Effects of phosphorylation of serine 40 of tyrosine hydroxylase on binding of catecholamines: evidence for a novel regulatory mechanism. Cerca con Google

Ren G., Wang X., Hao S., Hu H., Wang CC. J Bacteriol. 2007 Apr;189(7):2777-86. Translocation of alpha-synuclein expressed in Escherichia coli. Roskoski R Jr, Vulliet PR, Glass DB. J Neurochem. 1987 Mar;48(3):840-5. Phosphorylation of tyrosine hydroxylase by cyclic GMP-dependent protein kinase. Cerca con Google

Ruckert and Otting. J. Am. Chem 2000 Jun; 122, 7793-7797. Alignment of biological macromolecules in novel non-ionic liquid crystalline media for NMR experiment. Cerca con Google

Salzmann M, Pervushin K, Wider G, Senn H, Wüthrich K. Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13585-90. TROSY in triple-resonance experiments: new perspectives for sequential NMR assignment of large proteins. Cerca con Google

Salzmann M, Wider G, Pervushin K, Senn H, Wüthrich K.. J. Am. Chem. Soc. 1999 Nov, 121, 844-848. TROSY-type triple-resonance experiments for sequential assignments of large proteins. Cerca con Google

Sandal, M., Valle, F., Tessari, I., Mammi, S., Bergantino, E., Musiani, F., Brucale, M., Bubacco, L., and Samori, B. PLoS Biol. 2008; Conformational equilibria in monomeric alpha-synuclein at the single-molecule level. Cerca con Google

Sattler M., Schleucherb J., Griesinger C. Progress in Nuclear Magnetic Resonance Spectroscopy 1999; 34 93–158. Heteronuclear multidimensional NMR experiments for the structure determination of proteins in solution employing pulsed field gradients. Cerca con Google

Sato S, Chiba T, Sakata E, Kato K, Mizuno Y, Hattori N, Tanaka K. EMBO J. 2006 Jan 11;25(1):211-21. Cerca con Google

14-3-3eta is a novel regulator of parkin ubiquitin ligase. Cerca con Google

Schünemann V, Meier C, Meyer-Klaucke W, Winkler H, Trautwein AX, Knappskog PM, Toska K, Haavik J. J Biol Inorg Chem. 1999 Apr;4(2):223-31. Iron coordination geometry in full-length, truncated, and dehydrated forms of human tyrosine hydroxylase studied by Mössbauer and X-ray absorption spectroscopy. Cerca con Google

Sekimoto T, Fukumoto M, Yoneda Y. EMBO J. 2004 May 5;23(9):1934-42. 14-3-3 suppresses the nuclear localization of threonine 157-phosphorylated p27(Kip1). Cerca con Google

Segrest, J. P., Jones, M. K., De Loof, H., Brouillette, C. G., Venkatachalapathi, Y. V., and Anantharamaiah, G. M. J. Lipid Res. 1992; 33.141–166. The amphipathic helix in the exchangeable apolipoproteins: a review of secondary structure and function. Cerca con Google

Serpell, L. C., Berriman, J., Jakes, R., Goedert, M., and Crowther, R. A. Proc. Natl. Acad. Sci. U. S. A. 2000; 97, 4897–4902 Fiber diffraction of synthetic alpha synuclein filaments shows amyloid-like cross-beta Cerca con Google

conformation. Shilatifard A. Annu Rev Biochem. 2006;75:243-69. Chromatin modifications by methylation and ubiquitination: implications in the regulation of gene expression. Cerca con Google

Singleton, A. B., Farrer, M., Johnson, J., Singleton, A., Hague, et al. 2003 Science 302, 841 alpha-Synuclein locus triplication causes Parkinson’s disease. Cerca con Google

Spillantini, M. G., Crowther, R. A., Jakes, R., Cairns, N. J., Lantos, P. L., and Goedert, M. Neurosci. Lett. 1998; 251, 205–208. Cerca con Google

Filamentous alpha-synuclein inclusions link multiple system atrophy with Parkinson’s disease and dementia with Lewy bodies. Cerca con Google

Sutherland C, Alterio J, Campbell DG, Le Bourdellès B, Mallet J, Haavik J, Cohen. P Eur J Biochem. 1993 Oct 15;217(2):715-22. Cerca con Google

Phosphorylation and activation of human tyrosine hydroxylase in vitro by mitogenactivated protein (MAP) kinase and MAP-kinase-activated kinases 1 and 2. Cerca con Google

Swaans, R. J. M.; Rondot, P.; Renier, W. O.; van den Heuvel, L. P. W. J.; Steenbergen- Spanjers, G. C. H.; Wevers, R. A. Genet. 64: 25-31, 2000. Cerca con Google

Four novel mutations in the tyrosine hydroxylase gene in patients with infantile parkinsonism. Ann. Hum. Cerca con Google

Tehranian, R., Montoya, S. E., Van Laar, A. D., Hastings, T. G., and Perez, R. G. J. Neurochem.2006; 99, 1188–1196 Alpha-synuclein inhibits aromatic amino acid decarboxylase activity in dopaminergic cells. Cerca con Google

Tessari I, Bisaglia M, Valle F, Samorì B, Bergantino E, Mammi S, Bubacco L. J Biol Chem. 2008 Jun 13;283(24):16808-17. The reaction of alpha-synuclein with tyrosinase: possible implications for Parkinson disease. Cerca con Google

Thiru A, Nietlispach D, Mott HR, Okuwaki M, Lyon D, Nielsen PR, Hirshberg M,Verreault A, Murzina NV, Laue ED. EMBO J. 2004 Feb 11;23(3):489-99. Structural basis of HP1/PXVXL motif peptide interactions and HP1 localisation to heterochromatin. Cerca con Google

Tjandra N., Szabo A and Bax A. J. Am. Chem. Soc. 1996 Feb; 118, 6986-6991. Protein backbone dynamics and 15N chemical shift anisotropy from quantitative measurement of relaxation interference. Cerca con Google

Tompa, P. FEBS Lett.2005; 579, 3346–3354. The interplay between structure and function in intrinsically unstructured proteins. Cerca con Google

Tompkins, M. M., Basgall, E. J., Zamrini, E., and Hill, W. D. Am. J.Pathol. 1997; 150, 119– 131. Apoptotic-like changes in Lewy-body-associated disorders and normal aging in substantia nigral neurons. Cerca con Google

Torres GE, Yao WD, Mohn AR, Quan H, Kim KM, Levey AI, Staudinger J, Caron MG. Neuron. 2001 Apr;30(1):121-34. Functional interaction between monoamine plasma membrane transporters and the synaptic PDZ domain-containing protein PICK1. Cerca con Google

Toska K, Kleppe R, Armstrong CG, Morrice NA, Cohen P, Haavik J. J Neurochem. 2002 Nov;83(4):775-83. Cerca con Google

Regulation of tyrosine hydroxylase by stress-activated protein kinases. Cerca con Google

Toyo-oka K, Shionoya A, Gambello MJ, Cardoso C, Leventer R, Ward HL, Ayala R, Tsai LH, Dobyns W, Ledbetter D, Hirotsune S, Wynshaw-Boris A. Nat Genet. 2003 Jul;34(3):274-85. 14-3-3epsilon is important for neuronal migration by binding to NUDEL: a molecular explanation for Miller-Dieker syndrome. Cerca con Google

Truong AB, Masters SC, Yang H, Fu H. Proteins 2002;49:321–5. Role of the 14-3-3 C-terminal loop in ligand interaction. Cerca con Google

Tzivion G, Luo Z, Avruch J. Nature 1998;394:88–92. A dimeric 14-3-3 protein is an essential cofactor for Raf kinase activity. Cerca con Google

Ubl A, Berg D, Holzmann C, Krüger R, Berger K, Arzberger T, Bornemann A, Riess O. Brain Res Mol Brain Res. 2002 Dec;108(1-2):33-9. 14-3-3 protein is a component of Lewy bodies in Parkinson's disease-mutation analysis and association studies of 14-3-3 eta. Cerca con Google

Ueda, K., Fukushima, H., Masliah, E., Xia, Y., Iwai, A., Yoshimoto, M., Otero, D. A., Kondo, J., Ihara, Y., and Saitoh, T. Proc. Natl. Acad.Sci. U. S. A. 1993; 90, 11282–11286 Cerca con Google

Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease. Cerca con Google

Ulmer, T. S., Bax, A., Cole, N. B., and Nussbaum, R. L. J. Biol. Chem. 2005; 280, 9595– 9603. Structure and dynamics of micelle-bound human alpha synuclein. Cerca con Google

Uversky VN, Lee HJ, Li J, Fink AL, Lee SJ. J Biol Chem. 2001 Nov 23;276(47):43495-8. Stabilization of partially folded conformation during alpha-synuclein oligomerization in both purified and cytosolic preparations. Cerca con Google

Uversky, V. N. Protein Sci.2002; 11, 739–756. Natively unfolded proteins: a point where biology waits for physics. Cerca con Google

Van Heusden GP. IUBMB Life. 2005 Sep;57(9):623-9. 14-3-3 proteins: regulators of numerous eukaryotic proteins. Cerca con Google

Van Holde K, Zlatanova J. Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10548-55. Review. What determines the folding of the chromatin fiber? Cerca con Google

Vaynberg J, Qin J. Trends Biotechnol. 2006 Jan;24(1):22-7. Review. Weak protein-protein interactions as probed by NMR spectroscopy. Velyvis A, Vaynberg J, Yang Y, Vinogradova O, Zhang Y, Wu C, Qin J. Nat Struct Biol. 2003 Jul;10(7):558-64. Structural and functional insights into PINCH LIM4 domain-mediated integrin signaling. Cerca con Google

Vilar, M., Chou, H. T., Luhrs, T., Maji, S. K., Riek-Loher, D., Verel, R., Manning, G., Stahlberg, H., and Riek, R. Proc. Natl. Acad. Sci. U. S. A. 2008; 105, 8637–8642. The fold of alpha-synuclein fibrils. Cerca con Google

Volles, M. J., and Lansbury, P. T., Jr. Biochemistry 2002; 41, 4595–4602. Vesicle permeabilization by protofibrillar alpha-synuclein is sensitive to Parkinson’s disease-linked mutations and occurs by a pore-like mechanism. Cerca con Google

Vulliet PR, Woodgett JR, Cohen P. J Biol Chem. 1984 Nov 25;259(22):13680-3. Phosphorylation of tyrosine hydroxylase by calmodulin-dependent multiprotein kinase. Cerca con Google

Weinreb, P. H., Zhen, W., Poon, A. W., Conway, K. A., and Lansbury, P. T., Jr. Biochemistry 1996; 35, 13709–13715. NACP, a protein implicated in Alzheimer’s disease and learning, is natively unfolded. Cerca con Google

Wilker EW, Grant RA, Artim SC, Yaffe MB. J Biol Chem 2005;280:18891–8. A structural basis for 14-3-3sigma functional specificity. Cerca con Google

Wood, S. J., Wypych, J., Steavenson, S., Louis, J. C., Citron, M., and Biere, A. L. J. Biol. Chem. 1999; 274, 19509–19512. alpha-synuclein fibrillogenesis is nucleation- dependent. Implications for the pathogenesis Cerca con Google

of Parkinson’s disease. Cerca con Google

Wu YN, Vu ND, Wagner PD. Biochem J. 1992 Aug 1;285 ( Pt 3):697-700. Anti-(14-3-3 protein) antibody inhibits stimulation of noradrenaline (norepinephrine) secretion by chromaffin-cell cytosolic proteins. Cerca con Google

Xu J, Kao SY, Lee FJ, Song W, Jin LW, Yankner BA. Nat Med. 2002 Jun; 8(6):600-6. Dopamine-dependent neurotoxicity of alpha-synuclein: a mechanism for selective neurodegeneration in Parkinson disease. Cerca con Google

Yamauchi T, Nakata H, Fujisawa H.J Biol Chem. 1981 Jun 10;256(11):5404-9. A new activator protein that activates tryptophan 5-monooxygenase and tyrosine 3- monooxygenase in the presence of Ca2+-calmodulin-dependent protein kinase. Purification and characterization. Cerca con Google

Yang X, Lee WH, Sobott F, Papagrigoriou E, Robinson CV, Grossmann JG, Sundström M, Doyle DA, Elkins JM. PNAS U S A. 2006 Nov 14;103(46):17237-42 Structural basis for protein-protein interactions in the 14-3-3 protein family. Cerca con Google

Yang HY, Wen Y, Chen C, Lozano G, Lee MH. Mol Cell Biol. 2003 Oct;23(20):7096-107. 14-3-3 sigma positively regulates p53 and suppresses tumor growth. Cerca con Google

Yavich, L., Tanila, H., Vepsalainen, S., and Jakala, P. J. Neurosci. 2004; 24, 11165–11170 Role of alpha-synuclein in presynaptic dopamine recruitment. Cerca con Google

Yano M, Nakamuta S, Wu X, Okumura Y, Kido H..Mol Biol Cell. 2006 Nov;17(11):4769- Cerca con Google

79. A novel function of 14-3-3 protein: 14-3-3zeta is a heat-shock-related molecular chaperone that dissolves thermal-aggregated proteins. Cerca con Google

Ying J, Chill JH, Louis JM, Bax A. J Biomol NMR. 2007 Mar;37(3):195-204. Mixed-time parallel evolution in multiple quantum NMR experiments: sensitivity and resolution enhancement in heteronuclear NMR. Cerca con Google

Yip-Schneider MT, Miao W, Lin A, Barnard DS, Tzivion G, Marshall MS. Biochem J. 2000 Oct 1;351(Pt 1):151-9. Regulation of the Raf-1 kinase domain by phosphorylation and 14-3-3 association. Cerca con Google

Zarranz, J. J., Alegre, J., Gomez-Esteban, J. C., Lezcano, E., Ros, et al. Ann. Neurol.2004; 55, 164–173. Cerca con Google

The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Cerca con Google

Zhou Y, Gu G, Goodlett DR, Zhang T, Pan C, Montine TJ, Montine KS, Aebersold RH, Zhang J. J Biol Chem. 2004 Sep 10;279(37):39155-64. Analysis of alpha-synuclein-associated proteins by quantitative proteomics. Cerca con Google

Zhou W, Zhu M, Wilson MA, Petsko GA, Fink AL. J Mol Biol. 2006 Mar 3;356(4):1036- 48. The oxidation state of DJ-1 regulates its chaperone activity toward alpha-synuclein. Cerca con Google

Zweckstetter M. Nat Protoc. 2008;3(4):679-90. NMR: prediction of molecular alignment from structure using the PALES software. Cerca con Google

Zweckstetter M, Bax A. J Biomol NMR. 2001 Aug;20(4):365-77. Characterization of molecular alignment in aqueous suspensions of Pf1 bacteriophage. Cerca con Google

Zweckstetter M, Bax A. J Am Chem Soc. 2001 Sep 26;123(38):9490-1. Single-step determination of protein substructures using dipolar couplings: aid to structural genomics. Cerca con Google

Download statistics

Solo per lo Staff dell Archivio: Modifica questo record