2JJT

Structure of human CD47 in complex with human signal regulatory protein (SIRP) alpha

Summary for 2JJT

• Entry DOI: 10.2210/pdb2jjt/pdb
• Related: 2JJS 2UV3 2VSC
• Descriptor: TYROSINE-PROTEIN PHOSPHATASE NON-RECEPTOR TYPE SUBSTRATE 1, LEUKOCYTE SURFACE ANTIGEN CD47, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: signal regulatory protein alpha, immunoglobulin superfamily, transmembrane, phosphoprotein, paired receptor, polymorphism, glycoprotein, cell adhesion, pyrrolidone carboxylic acid, alternative splicing, immunoglobulin domain, sirp, cd47, sirpa, membrane, sh3-binding
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 4
• Total formula weight: 58202.98

Authors

Hatherley, D.,Graham, S.C.,Turner, J.,Harlos, K.,Stuart, D.I.,Barclay, A.N. (deposition date: 2008-04-22, release date: 2008-08-05, Last modification date: 2024-10-16)

Primary citation

Hatherley, D.,Graham, S.C.,Turner, J.,Harlos, K.,Stuart, D.I.,Barclay, A.N.
Paired receptor specificity explained by structures of signal regulatory proteins alone and complexed with CD47.
Mol. Cell, 31:266-277, 2008

PubMed 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 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.

PubMed: 18657508
DOI: 10.1016/j.molcel.2008.05.026

Experimental method

X-RAY DIFFRACTION (2.3 Å)