2yz1
Crystal structure of the ligand-binding domain of murine SHPS-1/SIRP alpha
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OverviewOverview
SRC homology 2 domain-containing protein tyrosine phosphatase substrate 1, (SHPS-1 or SIRPalpha/BIT) is an immunoglobulin (Ig) superfamily, transmembrane receptor and a member of the signal regulatory protein, (SIRP) family involved in cell-cell interaction. SHPS-1 binds to its, ligand CD47 to relay an inhibitory signal for cellular responses, whereas, SIRPbeta, an activating member of the same family, does not bind to CD47, despite sharing a highly homologous ligand-binding domain with SHPS-1. To, address the molecular basis for specific CD47 recognition by SHPS-1, we, present the crystal structure of the ligand-binding domain of murine, SHPS-1 (mSHPS-1). Folding topology revealed that mSHPS-1 adopts an I2-set, Ig fold, but its overall structure resembles IgV domains of antigen, receptors, although it has an extended loop structure (C'E loop), which, forms a dimer interface in the crystal. Site-directed mutagenesis studies, of mSHPS-1 identified critical residues for CD47 binding including sites, in the C'E loop and regions corresponding to complementarity-determining, regions of antigen receptors. The structural and functional features of, mSHPS-1 are consistent with the human SHPS-1 structure except that human, SHPS-1 has an additional beta-strand D. These results suggest that the, variable complementarity-determining region-like loop structures in the, binding surface of SHPS-1 are generally required for ligand recognition in, a manner similar to that of antigen receptors, which may explain the, diverse ligand-binding specificities of SIRP family receptors.
About this StructureAbout this Structure
2YZ1 is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
ReferenceReference
Structural Insight into the Specific Interaction between Murine SHPS-1/SIRPalpha and Its Ligand CD47., Nakaishi A, Hirose M, Yoshimura M, Oneyama C, Saito K, Kuki N, Matsuda M, Honma N, Ohnishi H, Matozaki T, Okada M, Nakagawa A, J Mol Biol. 2007 Nov 7;. PMID:18045614
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