1yzb: Difference between revisions

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[[Image:1yzb.gif|left|200px]]
{{Seed}}
[[Image:1yzb.png|left|200px]]


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{{STRUCTURE_1yzb|  PDB=1yzb  |  SCENE=  }}  
{{STRUCTURE_1yzb|  PDB=1yzb  |  SCENE=  }}  


'''Solution structure of the Josephin domain of Ataxin-3'''
===Solution structure of the Josephin domain of Ataxin-3===




==Overview==
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The Josephin domain plays an important role in the cellular functions of ataxin-3, the protein responsible for the neurodegenerative Machado-Joseph disease. We have determined the solution structure of Josephin and shown that it belongs to the family of papain-like cysteine proteases, sharing the highest degree of structural similarity with bacterial staphopain. A currently unique structural feature of Josephin is a flexible helical hairpin formed by a 32-residue insertion, which could determine substrate specificity. By using the Josephin structure and the availability of NMR chemical shift assignments, we have mapped the enzyme active site by using the typical cysteine protease inhibitors, transepoxysuccinyl-L-eucylamido-4-guanidino-butane (E-64) and [L-3-trans-(propylcarbamyl)oxirane-2-carbonyl]-L-isoleucyl-L-proline (CA-074). We also demonstrate that the specific interaction of Josephin with the ubiquitin-like domain of the ubiquitin- and proteasome-binding factor HHR23B involves complementary exposed hydrophobic surfaces. The structural similarity with other deubiquitinating enzymes suggests a model for the proteolytic enzymatic activity of ataxin-3.
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==About this Structure==
==About this Structure==
1YZB is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YZB OCA].  
1YZB is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YZB OCA].  


==Reference==
==Reference==
The solution structure of the Josephin domain of ataxin-3: structural determinants for molecular recognition., Nicastro G, Menon RP, Masino L, Knowles PP, McDonald NQ, Pastore A, Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10493-8. Epub 2005 Jul 14. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16020535 16020535]
The solution structure of the Josephin domain of ataxin-3: structural determinants for molecular recognition., Nicastro G, Menon RP, Masino L, Knowles PP, McDonald NQ, Pastore A, Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10493-8. Epub 2005 Jul 14. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16020535 16020535]
Assignment of the 1H, 13C, and 15N resonances of the Josephin domain of human ataxin-3., Nicastro G, Masino L, Frenkiel TA, Kelly G, McCormick J, Menon RP, Pastore A, J Biomol NMR. 2004 Dec;30(4):457-8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15630566 15630566]
Characterization of the structure and the amyloidogenic properties of the Josephin domain of the polyglutamine-containing protein ataxin-3., Masino L, Nicastro G, Menon RP, Dal Piaz F, Calder L, Pastore A, J Mol Biol. 2004 Dec 3;344(4):1021-35. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15544810 15544810]
Domain architecture of the polyglutamine protein ataxin-3: a globular domain followed by a flexible tail., Masino L, Musi V, Menon RP, Fusi P, Kelly G, Frenkiel TA, Trottier Y, Pastore A, FEBS Lett. 2003 Aug 14;549(1-3):21-5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12914917 12914917]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Pastore, A.]]
[[Category: Pastore, A.]]
[[Category: Papain-like fold]]
[[Category: Papain-like fold]]
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