2afj
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SPRY domain-containing SOCS box protein 2 (SSB-2)
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Structural highlights
FunctionSPSB2_MOUSE Probable substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity). Evolutionary Conservation![]() Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe four mammalian SPRY domain-containing SOCS box proteins (SSB-1 to SSB-4) are characterized by a C-terminal SOCS box and a central SPRY domain. We have determined the first SPRY-domain structure, as part of SSB-2, by NMR. This domain adopts a novel fold consisting of a beta-sandwich structure formed by two four-stranded antiparallel beta-sheets with a unique topology. We demonstrate that SSB-1, SSB-2 and SSB-4, but not SSB-3, bind prostate apoptosis response protein-4 (Par-4). Mutational analysis of SSB-2 loop regions identified conserved structural determinants for its interaction with Par-4 and the hepatocyte growth factor receptor, c-Met. Mutations in analogous loop regions of pyrin and midline-1 SPRY domains have been shown to cause Mediterranean fever and Opitz syndrome, respectively. Our findings provide a template for SPRY-domain structure and an insight into the mechanism of SPRY-protein interaction. The SPRY domain of SSB-2 adopts a novel fold that presents conserved Par-4-binding residues.,Masters SL, Yao S, Willson TA, Zhang JG, Palmer KR, Smith BJ, Babon JJ, Nicola NA, Norton RS, Nicholson SE Nat Struct Mol Biol. 2006 Jan;13(1):77-84. Epub 2005 Dec 20. PMID:16369487[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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This page was last modified 08:17, 15 May 2024.