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Title | Structural analysis of cancer-relevant TCR-CD3 and peptide-MHC complexes by cryoEM. |
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Journal, issue, pages | Nat Commun, Vol. 14, Issue 1, Page 2401, Year 2023 |
Publish date | Apr 26, 2023 |
Authors | Kei Saotome / Drew Dudgeon / Kiersten Colotti / Michael J Moore / Jennifer Jones / Yi Zhou / Ashique Rafique / George D Yancopoulos / Andrew J Murphy / John C Lin / William C Olson / Matthew C Franklin / |
PubMed Abstract | The recognition of antigenic peptide-MHC (pMHC) molecules by T-cell receptors (TCR) initiates the T-cell mediated immune response. Structural characterization is key for understanding the specificity ...The recognition of antigenic peptide-MHC (pMHC) molecules by T-cell receptors (TCR) initiates the T-cell mediated immune response. Structural characterization is key for understanding the specificity of TCR-pMHC interactions and informing the development of therapeutics. Despite the rapid rise of single particle cryoelectron microscopy (cryoEM), x-ray crystallography has remained the preferred method for structure determination of TCR-pMHC complexes. Here, we report cryoEM structures of two distinct full-length α/β TCR-CD3 complexes bound to their pMHC ligand, the cancer-testis antigen HLA-A2/MAGEA4 (230-239). We also determined cryoEM structures of pMHCs containing MAGEA4 (230-239) peptide and the closely related MAGEA8 (232-241) peptide in the absence of TCR, which provided a structural explanation for the MAGEA4 preference displayed by the TCRs. These findings provide insights into the TCR recognition of a clinically relevant cancer antigen and demonstrate the utility of cryoEM for high-resolution structural analysis of TCR-pMHC interactions. |
External links | Nat Commun / PubMed:37100770 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.65 - 3.4 Å |
Structure data | EMDB-28570, PDB-8es7: EMDB-28571, PDB-8es8: EMDB-28572, PDB-8es9: EMDB-28573, PDB-8esa: EMDB-28574, PDB-8esb: |
Chemicals | ChemComp-Y01: ChemComp-NAG: |
Source |
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Keywords | IMMUNE SYSTEM / TCR / membrane protein / CD3 / HLA / MHC / receptor |