2WNG

complete extracellular structure of human signal regulatory protein (SIRP) alpha

Summary for 2WNG

• Entry DOI: 10.2210/pdb2wng/pdb
• Related: 2JJS 2JJT 2UV3
• Descriptor: TYROSINE-PROTEIN PHOSPHATASE NON-RECEPTOR TYPE SUBSTRATE 1, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: signal regulatory protein alpha, immunoglobulin superfamily, phosphoprotein, disulfide bond, paired receptor, alternative splicing, immunoglobulin domain, sirp, cd47, sirpa, membrane, sh3-binding, polymorphism, glycoprotein, transmembrane, cell adhesion
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 36425.54

Authors

Hatherley, D.,Graham, S.C.,Harlos, K.,Stuart, D.I.,Barclay, A.N. (deposition date: 2009-07-09, release date: 2009-07-21, Last modification date: 2024-11-06)

Primary citation

Hatherley, D.,Graham, S.C.,Harlos, K.,Stuart, D.I.,Barclay, A.N.
Structure of Signal-Regulatory Protein Alpha: A Link to Antigen Receptor Evolution.
J.Biol.Chem., 284:26613-, 2009

PubMed Abstract: Signal-regulatory protein alpha (SIRPalpha) 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 SIRPalpha, comprising three immunoglobulin superfamily domains, by x-ray crystallography to 2.5 A 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-SIRPalpha 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 SIRPalpha (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.

PubMed: 19628875
DOI: 10.1074/JBC.M109.017566

Experimental method

X-RAY DIFFRACTION (2.49 Å)