SPRY Domain-Containing SOCS Box Protein 2: Crystal Structure and Residues Critical for Protein Binding
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- 作者：Zhihe Kuang ; Shenggen Yao ; Yibin Xu ; Rowena S. Lewis ; Andrew Low ; Seth L. Masters ; Tracy A. Willson ; Tatiana B. Kolesnik ; S ; ra E. Nicholson ; Thomas J.P. Garrett ; Raymond S. Norton
- 关键词：SPRY domain-containing SOCS box protein ; SSB-2 ; crystal structure ; NMR ; protein– ; protein interaction
- 刊名：Journal of Molecular Biology
- 出版年：2009
- 出版时间：27 February 2009
- 年：2009
- 卷：386
- 期：3
- 页码：662-674
- 全文大小：2498 K
文摘
The 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 β-sandwich, consisting of two seven-stranded β-sheets wrapped around a long loop that extends from the centre strands of the inner or concave β-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.