Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

CD47 is a widely distributed cell-surface protein that acts a marker of self through interactions of myeloid and neural cells. We describe the high-resolution X-ray crystallographic structures of the immunoglobulin superfamily domain of CD47 alone and in complex with the N-terminal ligand-binding domain of signal regulatory protein alpha (SIRPalpha). The unusual and convoluted interacting face of CD47, comprising the N terminus and loops at the end of the domain, intercalates with the corresponding regions in SIRPalpha. We have also determined structures of the N-terminal domains of SIRPbeta, SIRPbeta(2), and SIRPgamma; proteins that are closely related to SIRPalpha but bind CD47 with negligible or reduced affinity. These results explain the specificity of CD47 for the SIRP family of paired receptors in atomic detail. Analysis of SIRPalpha polymorphisms suggests that these, as well as the activating SIRPs, may have evolved to counteract pathogen binding to the inhibitory SIRPalpha receptor.

Original publication

DOI

10.1016/j.molcel.2008.05.026

Type

Journal article

Journal

Mol Cell

Publication Date

25/07/2008

Volume

31

Pages

266 - 277

Keywords

Amino Acid Sequence, Animals, Antigens, CD47, CHO Cells, Cell Communication, Cricetinae, Cricetulus, Crystallography, X-Ray, Macrophages, Models, Molecular, Molecular Sequence Data, Polymorphism, Genetic, Protein Binding, Protein Structure, Secondary, Protein Structure, Tertiary, Receptors, Immunologic