Polymorphisms in the human inhibitory signal-regulatory protein α do not affect binding to its ligand CD47.

ABSTRACT: CD47 is a widely distributed membrane protein that interacts with signal-regulatory protein α (SIRPα), an inhibitory receptor on myeloid cells that gives a "don't-eat-me" signal. Manipulation of the interaction is of considerable interest in the immunotherapy of cancer and in xenotransplantation. The amino-terminal ligand binding domain of SIRPα is highly polymorphic in contrast to the single Ig-like domain of CD47. There is confusion as to whether the polymorphisms will affect ligand binding, but this is an important point for this interaction and other paired receptors being considered as targets for therapy. We show by x-ray crystallography that one human SIRPα allele differing in 13 amino acid residues has a very similar binding site and that several different alleles all bind CD47 wit

SUBMITTER: Hatherley D 

PROVIDER: S-EPMC3974974 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature