2jy7
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= SQSTM1, ORCA, OSIL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= SQSTM1, ORCA, OSIL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2jy8|2JY8]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2jy7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jy7 OCA], [http://www.ebi.ac.uk/pdbsum/2jy7 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2jy7 RCSB]</span> | ||
}} | }} | ||
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[[Category: zinc-finger]] | [[Category: zinc-finger]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:02:32 2008'' |
Revision as of 01:02, 31 March 2008
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| Gene: | SQSTM1, ORCA, OSIL (Homo sapiens) | ||||||
| Related: | 2JY8
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
NMR structure of the ubiquitin associated (UBA) domain of p62 (SQSTM1). RDC refined
Overview
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.
About this Structure
2JY7 is a Single protein structure of sequence from Homo sapiens. Full crystallographic 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 Mon Mar 31 04:02:32 2008
Categories: Homo sapiens | Single protein | Layfield, R. | Long, J E. | Searle, M S. | Alternative splicing | Apoptosis | Cytoplasm | Differentiation | Disease mutation | Endosome | Helical bundle | Immune response | Metal-binding | Nucleus | Phosphoprotein | Polymorphism | Protein binding | Three helice | Ubiquitin associated domain | Ubiquitin binding | Zinc | Zinc-finger
