3ek9
SPRY Domain-containing SOCS Box Protein 2: Crystal Structure and Residues Critical for Protein Binding
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 (a sequence repeat in dual-specificity kinase splA and ryanodine receptors) domain-containing suppressor of cytokine signalling (SOCS) box proteins (SSB-1 to -4) are characterised by a C-terminal SOCS box and a central SPRY domain. The latter is a protein interaction module found in over 1600 proteins, with more than 70 encoded in the human genome. Here we report the crystal structure of the SPRY domain of murine SSB-2 and compare it with the SSB-2 solution structure and crystal structures of other B30.2/SPRY domain-containing family proteins. The structure is a bent beta-sandwich, consisting of two seven-stranded beta-sheets wrapped around a long loop that extends from the centre strands of the inner or concave beta-sheet; it closely matches those of GUSTAVUS and SSB-4. The structure is also similar to those of two recently determined Neuralized homology repeat (NHR) domains (also known as NEUZ domains), with detailed comparisons, suggesting that the NEUZ/NHR domains form a subclass of SPRY domains. The binding site on SSB-2 for the prostate apoptosis response-4 (Par-4) protein has been mapped in finer detail using mutational analyses. Moreover, SSB-1 was shown to have a Par-4 binding surface similar to that identified for SSB-2. Structural perturbations of SSB-2 induced by mutations affecting its interaction with Par-4 and/or c-Met have been characterised by NMR. These comparisons, in conjunction with previously published dynamics data from NMR relaxation studies and coarse-grained dynamics simulation using normal mode analysis, further refine our understanding of the structural basis for protein recognition of SPRY domain-containing proteins. SPRY domain-containing SOCS box protein 2: crystal structure and residues critical for protein binding.,Kuang Z, Yao S, Xu Y, Lewis RS, Low A, Masters SL, Willson TA, Kolesnik TB, Nicholson SE, Garrett TJ, Norton RS J Mol Biol. 2009 Feb 27;386(3):662-74. Epub 2009 Jan 6. PMID:19154741[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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