6jxr

Structure of human T cell receptor-CD3 complex

Loading... Status: waiting for Mol* initialization Structural highlights 6jxr is a 8 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: Electron Microscopy, Resolution 3.7Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease CD3Z_HUMAN Defects in CD247 are the cause of immunodeficiency due to defect in CD3-zeta (CD3ZID) [MIM:610163. An immunological deficiency characterized by T-cells impaired immune response to alloantigens, tetanus toxoid and mitogens. Function CD3Z_HUMAN Probable role in assembly and expression of the TCR complex as well as signal transduction upon antigen triggering. Publication Abstract from PubMed The alphabeta T cell receptor (TCR), in association with the CD3gammaepsilon-CD3deltaepsilon-CD3zetazeta signalling hexamer, is the primary determinant of T cell development and activation, and of immune responses to foreign antigens. The mechanism of assembly of the TCR-CD3 complex remains unknown. Here we report a cryo-electron microscopy structure of human TCRalphabeta in complex with the CD3 hexamer at 3.7 A resolution. The structure contains the complete extracellular domains and all the transmembrane helices of TCR-CD3. The octameric TCR-CD3 complex is assembled with 1:1:1:1 stoichiometry of TCRalphabeta:CD3gammaepsilon:CD3deltaepsilon:CD3zetazeta. Assembly of the extracellular domains of TCR-CD3 is mediated by the constant domains and connecting peptides of TCRalphabeta that pack against CD3gammaepsilon-CD3deltaepsilon, forming a trimer-like structure proximal to the plasma membrane. The transmembrane segment of the CD3 complex adopts a barrel-like structure formed by interaction of the two transmembrane helices of CD3zetazeta with those of CD3gammaepsilon and CD3deltaepsilon. Insertion of the transmembrane helices of TCRalphabeta into the barrel-like structure via both hydrophobic and ionic interactions results in transmembrane assembly of the TCR-CD3 complex. Together, our data reveal the structural basis for TCR-CD3 complex assembly, providing clues to TCR triggering and a foundation for rational design of immunotherapies that target the complex. Structural basis of assembly of the human T cell receptor-CD3 complex.,Dong, Zheng L, Lin J, Zhang B, Zhu Y, Li N, Xie S, Wang Y, Gao N, Huang Z Nature. 2019 Sep;573(7775):546-552. doi: 10.1038/s41586-019-1537-0. Epub 2019 Aug, 28. PMID:31461748 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also CD3 3D structures T-cell receptor 3D structures

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