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Paired receptor specificity explained by structures of signal regulatory proteins alone and complexed with CD47

DOI: 10.1016/j.molcel.2008.05.026 DOI Help

Authors: Debbie Hatherley (University of Oxford) , Jessie Turner (University of Oxford) , Neil Barclay (University of Oxford) , Dave Stuart (Diamond Light Source) , Karl Harlos (Wellcome Trust Centre for Human Genetics, University of Oxford) , Stephen Graham (University of Cambridge)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Molecular Cell , VOL 31 (2) , PAGES 266-277

State: Published (Approved)
Published: January 2008

Abstract: 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 Xray 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 (SIRP alpha). 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 SIRP alpha. We have also determined structures of the N-terminal domains of SIRP beta, SIRP beta(2), and SIRP gamma; proteins that are closely related to SIR alpha 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 SIRP alpha polymorphisms suggests that these, as well as the activating SIRPs, may have evolved to counteract pathogen binding to the inhibitory SIRP alpha receptor.

Journal Keywords: Paired Receptor Specificity Explained By Structures Of Signal Regulatory Proteins Alone And Complexed With Cd47

Subject Areas: Biology and Bio-materials


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