6JXR

Structure of human T cell receptor-CD3 complex

Summary for 6JXR

• Entry DOI: 10.2210/pdb6jxr/pdb
• EMDB information: 9895
• Descriptor: T-cell surface glycoprotein CD3 zeta chain, T-cell surface glycoprotein CD3 delta chain, T-cell surface glycoprotein CD3 epsilon chain, ... (6 entities in total)
• Functional Keywords: immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 184045.45

Authors

Dong, D.,Zheng, L.,Lin, J.,Zhu, Y.,Li, N.,Zhang, B.,Xie, S.,Zheng, J.,Wang, Y.,Gao, N.,Huang, Z. (deposition date: 2019-04-24, release date: 2019-09-11, Last modification date: 2024-10-23)

Primary citation

Zheng, L.,Lin, J.,Zhang, B.,Zhu, Y.,Li, N.,Xie, S.,Wang, Y.,Gao, N.,Huang, Z.
Structural basis of assembly of the human T cell receptor-CD3 complex.
Nature, 573:546-552, 2019

PubMed Abstract: 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.

PubMed: 31461748
DOI: 10.1038/s41586-019-1537-0

Experimental method

ELECTRON MICROSCOPY (3.7 Å)