This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
2aga
From Proteopedia
(New page: 200px<br /> <applet load="2aga" size="450" color="white" frame="true" align="right" spinBox="true" caption="2aga" /> '''De-ubiquitinating function of ataxin-3: ins...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:2aga.gif|left|200px]]<br /> | + | [[Image:2aga.gif|left|200px]]<br /><applet load="2aga" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2aga" size=" | + | |
caption="2aga" /> | caption="2aga" /> | ||
'''De-ubiquitinating function of ataxin-3: insights from the solution structure of the Josephin domain'''<br /> | '''De-ubiquitinating function of ataxin-3: insights from the solution structure of the Josephin domain'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Spinocerebellar ataxia type 3 is a human neurodegenerative disease | + | Spinocerebellar ataxia type 3 is a human neurodegenerative disease resulting from polyglutamine tract expansion. The affected protein, ataxin-3, which contains an N-terminal Josephin domain followed by tandem ubiquitin (Ub)-interacting motifs (UIMs) and a polyglutamine stretch, has been implicated in the function of the Ub proteasome system. NMR-based structural analysis has now revealed that the Josephin domain binds Ub and has a papain-like fold that is reminiscent of that of other deubiquitinases, despite primary sequence divergence but consistent with its deubiqutinating activity. Mutation of the catalytic Cys enhances the stability of a complex between ataxin-3 and polyubiquitinated proteins. This effect depends on the integrity of the UIM region, suggesting that the UIMs are bound to the substrate polyubiquitin during catalysis. We propose that ataxin-3 functions as a polyubiquitin chain-editing enzyme. |
==Disease== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2AGA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 2AGA is a [http://en.wikipedia.org/wiki/Single_protein 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=2AGA OCA]. |
==Reference== | ==Reference== | ||
| Line 17: | Line 16: | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Camilli, P | + | [[Category: Camilli, P De.]] |
| - | [[Category: Fiore, P | + | [[Category: Fiore, P Di.]] |
| - | [[Category: Hodsdon, M | + | [[Category: Hodsdon, M E.]] |
[[Category: Mao, Y.]] | [[Category: Mao, Y.]] | ||
[[Category: Polo, S.]] | [[Category: Polo, S.]] | ||
| Line 29: | Line 28: | ||
[[Category: vcp/p97]] | [[Category: vcp/p97]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:27:09 2008'' |
Revision as of 14:27, 21 February 2008
|
De-ubiquitinating function of ataxin-3: insights from the solution structure of the Josephin domain
Contents |
Overview
Spinocerebellar ataxia type 3 is a human neurodegenerative disease resulting from polyglutamine tract expansion. The affected protein, ataxin-3, which contains an N-terminal Josephin domain followed by tandem ubiquitin (Ub)-interacting motifs (UIMs) and a polyglutamine stretch, has been implicated in the function of the Ub proteasome system. NMR-based structural analysis has now revealed that the Josephin domain binds Ub and has a papain-like fold that is reminiscent of that of other deubiquitinases, despite primary sequence divergence but consistent with its deubiqutinating activity. Mutation of the catalytic Cys enhances the stability of a complex between ataxin-3 and polyubiquitinated proteins. This effect depends on the integrity of the UIM region, suggesting that the UIMs are bound to the substrate polyubiquitin during catalysis. We propose that ataxin-3 functions as a polyubiquitin chain-editing enzyme.
Disease
Known diseases associated with this structure: Machado-Joseph disease OMIM:[607047]
About this Structure
2AGA is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Deubiquitinating function of ataxin-3: insights from the solution structure of the Josephin domain., Mao Y, Senic-Matuglia F, Di Fiore PP, Polo S, Hodsdon ME, De Camilli P, Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12700-5. Epub 2005 Aug 23. PMID:16118278
Page seeded by OCA on Thu Feb 21 16:27:09 2008
Categories: Homo sapiens | Single protein | Camilli, P De. | Fiore, P Di. | Hodsdon, M E. | Mao, Y. | Polo, S. | Senic-Matuglia, F. | Ataxia | Polyglutamine | Ubiquitin | Uim | Vcp/p97
