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| [[Image:2jy7.jpg|left|200px]] | | {{Seed}} |
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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'''
| | ===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. | | The line below this paragraph, {{ABSTRACT_PUBMED_18083707}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 18083707 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_18083707}} |
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| ==About this Structure== | | ==About this Structure== |
| 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]. | | 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]. |
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| ==Reference== | | ==Reference== |
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| [[Category: Zinc]] | | [[Category: Zinc]] |
| [[Category: Zinc-finger]] | | [[Category: Zinc-finger]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 09:23:29 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 15:33:41 2008'' |
