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The SPRY domain of SSB-2 adopts a novel fold that presents conserved Par-4-binding residues


Masters, SL; Yao, SG; Willson, TA; Zhang, JG; Palmer, KR; Smith, BJ; Babon, JJ; Nicola, NA; Norton, RS; Nicholson, SE
2006-01
NATURE STRUCTURAL & MOLECULAR BIOLOGY
Journal Article
13
1
77-84
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.
NATURE PUBLISHING GROUP
FAMILIAL MEDITERRANEAN FEVER; OPITZ G/BBB SYNDROME; BOX PROTEIN-2 SSB-2; SOCS-BOX; B30.2-LIKE DOMAIN; BACKBONE DYNAMICS; GENE; CYTOKINE; NMR; SUPPRESSORS
10.1038/nsmb1034
Refer to copyright notice on published article.

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Creation Date 2006-01-01 12:00:00