5fn7

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Crystal structure of human CD45 extracellular region, domains d1-d2

Structural highlights

5fn7 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.3Å
Ligands:HG, NAG
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

PTPRC_HUMAN T-B+ severe combined immunodeficiency due to CD45 deficiency. The disease is caused by mutations affecting the gene represented in this entry. Disease susceptibility may be associated with variations affecting the gene represented in this entry.

Function

PTPRC_HUMAN Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor. Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first PTPase domain has enzymatic activity, while the second one seems to affect the substrate specificity of the first one. Upon T-cell activation, recruits and dephosphorylates SKAP1 and FYN. Dephosphorylates LYN, and thereby modulates LYN activity (By similarity).

Publication Abstract from PubMed

It has been proposed that the local segregation of kinases and the tyrosine phosphatase CD45 underpins T cell antigen receptor (TCR) triggering, but how such segregation occurs and whether it can initiate signaling is unclear. Using structural and biophysical analysis, we show that the extracellular region of CD45 is rigid and extends beyond the distance spanned by TCR-ligand complexes, implying that sites of TCR-ligand engagement would sterically exclude CD45. We also show that the formation of 'close contacts', new structures characterized by spontaneous CD45 and kinase segregation at the submicron-scale, initiates signaling even when TCR ligands are absent. Our work reveals the structural basis for, and the potent signaling effects of, local CD45 and kinase segregation. TCR ligands have the potential to heighten signaling simply by holding receptors in close contacts.

Initiation of T cell signaling by CD45 segregation at 'close contacts'.,Chang VT, Fernandes RA, Ganzinger KA, Lee SF, Siebold C, McColl J, Jonsson P, Palayret M, Harlos K, Coles CH, Jones EY, Lui Y, Huang E, Gilbert RJ, Klenerman D, Aricescu AR, Davis SJ Nat Immunol. 2016 May;17(5):574-82. doi: 10.1038/ni.3392. Epub 2016 Mar 21. PMID:26998761[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
52 reviews cite this structure
TCR Signaling: Mechanisms of Initiation and Propagation.
Courtney et al. (2018)
51 more
109 other articles
No citations found

See Also

References

  1. ↑ Chang VT, Fernandes RA, Ganzinger KA, Lee SF, Siebold C, McColl J, Jonsson P, Palayret M, Harlos K, Coles CH, Jones EY, Lui Y, Huang E, Gilbert RJ, Klenerman D, Aricescu AR, Davis SJ. Initiation of T cell signaling by CD45 segregation at 'close contacts'. Nat Immunol. 2016 May;17(5):574-82. doi: 10.1038/ni.3392. Epub 2016 Mar 21. PMID:26998761 doi:http://dx.doi.org/10.1038/ni.3392

Contents


PDB ID 5fn7

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OCA

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