3EK9

SPRY Domain-containing SOCS Box Protein 2: Crystal Structure and Residues Critical for Protein Binding

Summary for 3EK9

• Entry DOI: 10.2210/pdb3ek9/pdb
• Descriptor: SPRY domain-containing SOCS box protein 2, GLYCEROL (3 entities in total)
• Functional Keywords: spry domain, ubl conjugation pathway, signaling protein, protein binding
• Biological source: Mus musculus (Mouse)
• Cellular location: Cytoplasm (Probable): O88838
• Total number of polymer chains: 1
• Total formula weight: 23457.25

Authors

Kuang, Z.,Yao, S.,Xu, Y.,Garrett, T.J.P.,Norton, R.S. (deposition date: 2008-09-19, release date: 2009-02-24, Last modification date: 2023-08-30)

Primary citation

Kuang, Z.,Yao, S.,Xu, Y.,Lewis, R.S.,Low, A.,Masters, S.L.,Willson, T.A.,Kolesnik, T.B.,Nicholson, S.E.,Garrett, T.J.,Norton, R.S.
SPRY domain-containing SOCS box protein 2: crystal structure and residues critical for protein binding.
J.Mol.Biol., 386:662-674, 2009

PubMed Abstract: 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 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.

PubMed: 19154741
DOI: 10.1016/j.jmb.2008.12.078

Experimental method

X-RAY DIFFRACTION (2.6 Å)