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TitleStructural basis of assembly of the human T cell receptor-CD3 complex.
Journal, issue, pagesNature, Vol. 573, Issue 7775, Page 546-552, Year 2019
Publish dateAug 28, 2019
AuthorsDe Dong / Lvqin Zheng / Jianquan Lin / Bailing Zhang / Yuwei Zhu / Ningning Li / Shuangyu Xie / Yuhang Wang / Ning Gao / Zhiwei Huang /
PubMed AbstractThe αβ T cell receptor (TCR), in association with the CD3γε-CD3δε-CD3ζζ signalling hexamer, is the primary determinant of T cell development and activation, and of immune responses to foreign ...The αβ T cell receptor (TCR), in association with the CD3γε-CD3δε-CD3ζζ 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 TCRαβ in complex with the CD3 hexamer at 3.7 Å 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 TCRαβ:CD3γε:CD3δε:CD3ζζ. Assembly of the extracellular domains of TCR-CD3 is mediated by the constant domains and connecting peptides of TCRαβ that pack against CD3γε-CD3δε, 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 CD3ζζ with those of CD3γε and CD3δε. Insertion of the transmembrane helices of TCRαβ 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.
External linksPubMed:31461748 / Publisher's page
KeywordsCryoelectron Microscopy / Humans / Models, Molecular / Protein Domains / Protein Structure, Quaternary / Receptor-CD3 Complex, Antigen, T-Cell / IMMUNE SYSTEM
MethodsEM (single particle)
Resolution3.7 A
Structure data

EMDB-9895:
Structure of human T cell receptor-CD3 complex

PDB-6jxr:
Structure of human T cell receptor-CD3 complex

Source
  • homo sapiens (human)

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