2aga

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(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...)
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'''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==
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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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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==
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==About this Structure==
==About this Structure==
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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://ispc.weizmann.ac.il/oca-bin/ocashort?id=2AGA OCA].
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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==
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Camilli, P.De.]]
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[[Category: Camilli, P De.]]
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[[Category: Fiore, P.Di.]]
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[[Category: Fiore, P Di.]]
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[[Category: Hodsdon, M.E.]]
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[[Category: Hodsdon, M E.]]
[[Category: Mao, Y.]]
[[Category: Mao, Y.]]
[[Category: Polo, S.]]
[[Category: Polo, S.]]
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[[Category: vcp/p97]]
[[Category: vcp/p97]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:51:03 2007''
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''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

Image:2aga.gif

2aga

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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

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