2YZ1

Crystal structure of the ligand-binding domain of murine SHPS-1/SIRP alpha

Summary for 2YZ1

• Entry DOI: 10.2210/pdb2yz1/pdb
• Descriptor: Tyrosine-protein phosphatase non-receptor type substrate 1 (2 entities in total)
• Functional Keywords: beta-sandwich, structural genomics, nppsfa, national project on protein structural and functional analyses, alternative splicing, glycoprotein, immunoglobulin domain, membrane, phosphorylation, polymorphism, sh3-binding, transmembrane, immune system
• Biological source: Mus musculus (house mouse)
• Cellular location: Membrane; Single-pass type I membrane protein: P97797
• Total number of polymer chains: 2
• Total formula weight: 26027.23

Authors

Nakaishi, A. (deposition date: 2007-05-02, release date: 2007-12-11, Last modification date: 2024-11-20)

Primary citation

Nakaishi, A.,Hirose, M.,Yoshimura, M.,Oneyama, C.,Saito, K.,Kuki, N.,Matsuda, M.,Honma, N.,Ohnishi, H.,Matozaki, T.,Okada, M.,Nakagawa, A.
Structural insight into the specific interaction between murine SHPS-1/SIRP alpha and its ligand CD47
J.Mol.Biol., 375:650-660, 2008

PubMed Abstract: SRC homology 2 domain-containing protein tyrosine phosphatase substrate 1 (SHPS-1 or SIRP alpha/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.

PubMed: 18045614
DOI: 10.1016/j.jmb.2007.10.085

Experimental method

X-RAY DIFFRACTION (1.4 Å)