2wng
complete extracellular structure of human signal regulatory protein (SIRP) alphacomplete extracellular structure of human signal regulatory protein (SIRP) alpha
Structural highlights
FunctionSHPS1_HUMAN Immunoglobulin-like cell surface receptor for CD47. Acts as docking protein and induces translocation of PTPN6, PTPN11 and other binding partners from the cytosol to the plasma membrane. Supports adhesion of cerebellar neurons, neurite outgrowth and glial cell attachment. May play a key role in intracellular signaling during synaptogenesis and in synaptic function (By similarity). Involved in the negative regulation of receptor tyrosine kinase-coupled cellular responses induced by cell adhesion, growth factors or insulin. Mediates negative regulation of phagocytosis, mast cell activation and dendritic cell activation. CD47 binding prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedSignal-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. Structure of signal-regulatory protein alpha: a link to antigen receptor evolution.,Hatherley D, Graham SC, Harlos K, Stuart DI, Barclay AN J Biol Chem. 2009 Sep 25;284(39):26613-9. Epub 2009 Jul 23. PMID:19628875[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||