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Signal regulatory protein (SIRP) alpha is a membrane receptor that sends inhibitory signals to myeloid cells by engagement of CD47. The high resolution x-ray structure of the N-terminal ligand binding domain shows it to have a distinctive immunoglobulin superfamily V-like fold. Site-directed mutagenesis suggests that CD47 is bound at a surface involving the BC, FG, and DE loops, which distinguishes it from other immunoglobulin superfamily surface proteins that use the faces of the fold, but resembles antigen receptors. The SIRP interaction is confined to a single domain, and its use of an extended DE loop strengthens the similarity with T cell receptor binding and the suggestion that they are closely related in evolution. The employment of loops to form the CD47-binding surface provides a mechanism for small sequence changes to modulate binding specificity, explaining the different binding properties of SIRP family members.

Original publication

DOI

10.1074/jbc.M611511200

Type

Journal article

Journal

J Biol Chem

Publication Date

11/05/2007

Volume

282

Pages

14567 - 14575

Keywords

Amino Acid Sequence, Antigens, CD47, Antigens, Differentiation, Binding Sites, Crystallography, X-Ray, Humans, Ligands, Macrophages, Molecular Sequence Data, Mutagenesis, Site-Directed, Protein Conformation, Protein Folding, Receptors, Antigen, T-Cell, Receptors, Immunologic, Sequence Homology, Amino Acid