2jy7

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{{STRUCTURE_2jy7| PDB=2jy7 | SCENE= }}
{{STRUCTURE_2jy7| PDB=2jy7 | SCENE= }}
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'''NMR structure of the ubiquitin associated (UBA) domain of p62 (SQSTM1). RDC refined'''
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===NMR structure of the ubiquitin associated (UBA) domain of p62 (SQSTM1). RDC refined===
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==Overview==
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The p62 protein functions as a scaffold in signaling pathways that lead to activation of NF-kappaB and is an important regulator of osteoclastogenesis. Mutations affecting the receptor activator of NF-kappaB signaling axis can result in human skeletal disorders, including those identified in the C-terminal ubiquitin-associated (UBA) domain of p62 in patients with Paget disease of bone. These observations suggest that the disease may involve a common mechanism related to alterations in the ubiquitin-binding properties of p62. The structural basis for ubiquitin recognition by the UBA domain of p62 has been investigated using NMR and reveals a novel binding mechanism involving a slow exchange structural reorganization of the UBA domain to a "bound" non-canonical UBA conformation that is not significantly populated in the absence of ubiquitin. The repacking of the three-helix bundle generates a binding surface localized around the conserved Xaa-Gly-Phe-Xaa loop that appears to optimize both hydrophobic and electrostatic surface complementarity with ubiquitin. NMR titration analysis shows that the p62-UBA binds to Lys(48)-linked di-ubiquitin with approximately 4-fold lower affinity than to mono-ubiquitin, suggesting preferential binding of the p62-UBA to single ubiquitin units, consistent with the apparent in vivo preference of the p62 protein for Lys(63)-linked polyubiquitin chains (which adopt a more open and extended structure). The conformational switch observed on binding may represent a novel mechanism that underlies specificity in regulating signalinduced protein recognition events.
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{{ABSTRACT_PUBMED_18083707}}
==About this Structure==
==About this Structure==
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2JY7 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=2JY7 OCA].
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2JY7 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=2JY7 OCA].
==Reference==
==Reference==
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[[Category: Zinc]]
[[Category: Zinc]]
[[Category: Zinc-finger]]
[[Category: Zinc-finger]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 09:23:29 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 15:33:41 2008''

Revision as of 12:33, 29 July 2008

Image:2jy7.png

Template:STRUCTURE 2jy7

NMR structure of the ubiquitin associated (UBA) domain of p62 (SQSTM1). RDC refined

Template:ABSTRACT PUBMED 18083707

About this Structure

2JY7 is a Single protein structure of sequence from Homo sapiens. Full experimental information is available from OCA.

Reference

Ubiquitin Recognition by the Ubiquitin-associated Domain of p62 Involves a Novel Conformational Switch., Long J, Gallagher TR, Cavey JR, Sheppard PW, Ralston SH, Layfield R, Searle MS, J Biol Chem. 2008 Feb 29;283(9):5427-5440. Epub 2007 Dec 14. PMID:18083707

Page seeded by OCA on Tue Jul 29 15:33:41 2008

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