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Structure of Signal-regulatory Protein: A LINK TO ANTIGEN RECEPTOR EVOLUTION

DOI: 10.1074/jbc.M109.017566 DOI Help

Authors: Debbie Hatherley (University of Oxford) , Stephen C. Graham (University of Oxford) , Karl Harlos (Wellcome Trust Centre for Human Genetics, University of Oxford) , David I. Stuart (University of Oxford) , A. Neil Barclay (University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Biological Chemistry , VOL 284 , PAGES 26613-26619.

State: Published (Approved)
Published: July 2009

Abstract: Signal-regulatory protein alpha (SIRP alpha) is a myeloid membrane receptor that interacts with the membrane protein CD47, a marker of self. We have solved the structure of the complete extracellular portion of SIRP alpha, comprising three immunoglobulin superfamily domains, by x-ray crystallography to 2.5 Å resolution. These data, together with previous data on the N-terminal domain and its ligand CD47 (possessing a single immunoglobulin superfamily domain), show that the CD47-SIRP alpha interaction will span a distance of around 14 nm between interacting cells, comparable with that of an immunological synapse. The N-terminal (V-set) domain mediates binding to CD47, and the two others are found to be constant (C1-set) domains. C1-set domains are restricted to proteins involved in vertebrate antigen recognition: T cell antigen receptors, immunoglobulins, major histocompatibility complex antigens, tapasin, and beta2-microglobulin. The domains of SIRP alpha (domains 2 and 3) are structurally more similar to C1-set domains than any cell surface protein not involved in antigen recognition. This strengthens the suggestion from sequence analysis that SIRP is evolutionarily closely related to antigen recognition proteins.

Subject Areas: Biology and Bio-materials

Facility: ESRF

Added On: 25/06/2010 09:59

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