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8es8

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CryoEM structure of PN45545 TCR-CD3 in complex with HLA-A2 MAGEA4 (230-239)

Structural highlights

8es8 is a 11 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 2.65Å
Ligands:	, ,
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.^[1]

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 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 alpha/beta 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.

Structural analysis of cancer-relevant TCR-CD3 and peptide-MHC complexes by cryoEM.,Saotome K, Dudgeon D, Colotti K, Moore MJ, Jones J, Zhou Y, Rafique A, Yancopoulos GD, Murphy AJ, Lin JC, Olson WC, Franklin MC Nat Commun. 2023 Apr 26;14(1):2401. doi: 10.1038/s41467-023-37532-7. PMID:37100770^[2]

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

References

↑ Rieux-Laucat F, Hivroz C, Lim A, Mateo V, Pellier I, Selz F, Fischer A, Le Deist F. Inherited and somatic CD3zeta mutations in a patient with T-cell deficiency. N Engl J Med. 2006 May 4;354(18):1913-21. PMID:16672702 doi:354/18/1913
↑ Saotome K, Dudgeon D, Colotti K, Moore MJ, Jones J, Zhou Y, Rafique A, Yancopoulos GD, Murphy AJ, Lin JC, Olson WC, Franklin MC. Structural analysis of cancer-relevant TCR-CD3 and peptide-MHC complexes by cryoEM. Nat Commun. 2023 Apr 26;14(1):2401. PMID:37100770 doi:10.1038/s41467-023-37532-7