Structure and interactions of SSB-2
Z Kuang, S Yao, A Low, JJ Babon, TJP Garrett, RS Norton (Structural Biology), SL Masters, TA Willson, J-G Zhang, NA Nicola, SE Nicholson (Cancer and Haematology) [Nat Struct Mol Biol 2006 Jan;13(1):77-84 PMID:16369487 229. Kuang Z, Yao S, Xu Y, Lewis RS, Low A, Masters SL, Willson TA, Kolesnik TB, Nicholson SE, Garrett TJP & Norton RS (2009) SPRY domain-containing SOCS box protein 2: crystal structure and residues critical for protein binding. Journal of Molecular Biology 386, 662–674.
The SPRY domain-containing SOCS box protein 2 (SSB-2) is one of a sub-family of four proteins (SSB-1 to -4) within the SOCS protein family. Like other central domains in SOCS proteins, the SPRY domain is expected to mediate protein-protein interactions. It has since been shown that SSB proteins interact directly with hepatocyte growth factor (HGF) c-Met. Furthermore, interactions with Par-4 (prostate apoptosis response-4) through the SPRY domain of SSB proteins have also been observed. We have solved the structure of SSB2 in solution using NMR spectroscopy and subsequently by X-ray crystallography. The SSB-2 structure represents the first 3D structure of a SPRY domain. Residues responsible for Par-4 binding are located predominantly in two loop regions. Further studies are underway to map the interactive surfaces with other partners onto our 3D structure.
Recently we have identified another biologically relevant binding partner for the SSB proteins and are exploring the role of this interaction in controlling the body’s response to infectious diseases.
