1q02
From Proteopedia
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| - | [[Image:1q02.gif|left|200px]] | + | [[Image:1q02.gif|left|200px]] |
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| - | '''NMR structure of the UBA domain of p62 (SQSTM1)''' | + | {{Structure |
| + | |PDB= 1q02 |SIZE=350|CAPTION= <scene name='initialview01'>1q02</scene> | ||
| + | |SITE= | ||
| + | |LIGAND= | ||
| + | |ACTIVITY= | ||
| + | |GENE= | ||
| + | }} | ||
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| + | '''NMR structure of the UBA domain of p62 (SQSTM1)''' | ||
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==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1Q02 is a [ | + | 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]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/12857745 12857745] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: helical bundle]] | [[Category: helical bundle]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:31:14 2008'' |
Revision as of 11:31, 20 March 2008
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NMR structure of the UBA domain of p62 (SQSTM1)
Contents |
Overview
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 --> 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 --> 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.
Disease
Known disease associated with this structure: Paget disease of bone OMIM:[601530]
About this Structure
1Q02 is a Single protein structure of sequence from Homo sapiens. Full crystallographic 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
Page seeded by OCA on Thu Mar 20 13:31:14 2008
