2aga
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= ATXN3, ATX3, MJD, MJD1, SCA3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= ATXN3, ATX3, MJD, MJD1, SCA3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2aga FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aga OCA], [http://www.ebi.ac.uk/pdbsum/2aga PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2aga RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Machado-Joseph disease OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607047 607047]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: vcp/p97]] | [[Category: vcp/p97]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:52:19 2008'' |
Revision as of 22:52, 30 March 2008
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| Gene: | ATXN3, ATX3, MJD, MJD1, SCA3 (Homo sapiens) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
De-ubiquitinating function of ataxin-3: insights from the solution structure of the Josephin domain
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.
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 Mon Mar 31 01:52:19 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
