The SPRY domain of SSB-2 adopts a novel fold that presents conserved Par-4-binding residues
- Author(s)
- Masters, SL; Yao, SG; Willson, TA; Zhang, JG; Palmer, KR; Smith, BJ; Babon, JJ; Nicola, NA; Norton, RS; Nicholson, SE;
- Details
- Publication Year 2006-01,Volume 13,Issue #1,Page 77-84
- Journal Title
- NATURE STRUCTURAL & MOLECULAR BIOLOGY
- Publication Type
- Journal Article
- Abstract
- 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.
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- FAMILIAL MEDITERRANEAN FEVER; OPITZ G/BBB SYNDROME; BOX PROTEIN-2 SSB-2; SOCS-BOX; B30.2-LIKE DOMAIN; BACKBONE DYNAMICS; GENE; CYTOKINE; NMR; SUPPRESSORS
- Publisher's Version
- https://doi.org/10.1038/nsmb1034
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2006-01-01 12:00:00