2afj

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2afj

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SPRY domain-containing SOCS box protein 2 (SSB-2)

Overview

The 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.

About this Structure

2AFJ is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.

Reference

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

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