1q02

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{{STRUCTURE_1q02| PDB=1q02 | SCENE= }}
{{STRUCTURE_1q02| PDB=1q02 | SCENE= }}
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'''NMR structure of the UBA domain of p62 (SQSTM1)'''
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===NMR structure of the UBA domain of p62 (SQSTM1)===
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==Overview==
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The p62 protein (also known as SQSTM1) mediates diverse cellular functions including control of NFkappaB signaling and transcriptional activation. p62 binds non-covalently to ubiquitin and co-localizes with ubiquitylated inclusions in a number of human protein aggregation diseases. Mutations in the gene encoding p62 cause Paget's disease of bone (PDB), a common disorder of the elderly characterized by excessive bone resorption and formation. All of the p62 PDB mutations identified to date cluster within the C-terminal region of the protein, which shows low sequence identity to previously characterized ubiquitin-associated (UBA) domains. We report the first NMR structure of a recombinant polypeptide that contains the C-terminal UBA domain of the human p62 protein (residues 387-436). This sequence, which confers multiubiquitin chain binding, forms a compact three-helix bundle with a structure analogous to the UBA domains of HHR23A but with differences in the loop regions connecting helices that may be involved in binding accessory proteins. We show that the Pro392 --&gt; Leu PDB substitution mutation modifies the structure of the UBA domain by extending the N terminus of helix 1. In contrast to the p62 PDB deletion mutations that remove the UBA domain and ablate multiubiquitin chain binding, the Pro392 --&gt; Leu substitution does not affect interaction of the UBA domain with multiubiquitin chains. Thus, phenotypically identical substitution and deletion mutations do not appear to predispose to PDB through a mechanism dependent on a common loss of ubiquitin chain binding by p62.
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{{ABSTRACT_PUBMED_12857745}}
==About this Structure==
==About this Structure==
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1Q02 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=1Q02 OCA].
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1Q02 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=1Q02 OCA].
==Reference==
==Reference==
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[[Category: Sheppard, P W.]]
[[Category: Sheppard, P W.]]
[[Category: Helical bundle]]
[[Category: Helical bundle]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 05:42:07 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 07:22:15 2008''

Revision as of 04:22, 28 July 2008

Image:1q02.png

Template:STRUCTURE 1q02

NMR structure of the UBA domain of p62 (SQSTM1)

Template:ABSTRACT PUBMED 12857745

About this Structure

1Q02 is a Single protein structure of sequence from Homo sapiens. Full experimental information is available from OCA.

Reference

Structure of the ubiquitin-associated domain of p62 (SQSTM1) and implications for mutations that cause Paget's disease of bone., Ciani B, Layfield R, Cavey JR, Sheppard PW, Searle MS, J Biol Chem. 2003 Sep 26;278(39):37409-12. Epub 2003 Jul 11. PMID:12857745

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