6tmo | pdb_00006tmo

Structure determination of an enhanced affinity TCR, a24b17, in complex with HLA-A*02:01 presenting a MART-1 peptide, EAAGIGILTV

spinqualitylabelsall models 6tmo, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6tmo is a 5 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: X-ray diffraction, Resolution 2.1Å Ligands: EDO, GOL, SO4, TAM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A5B8RNS7_HUMAN Publication Abstract from PubMed Immuno-oncology approaches that utilize T cell receptors (TCRs) are becoming highly attractive because of their potential to target virtually all cellular proteins, including cancer-specific epitopes, via the recognition of peptide-human leukocyte antigen (pHLA) complexes presented at the cell surface. However, because natural TCRs generally recognize cancer-derived pHLAs with very weak affinities, efforts have been made to enhance their binding strength, in some cases by several million-fold. In this study, we investigated the mechanisms underpinning human TCR affinity enhancement by comparing the crystal structures of engineered enhanced affinity TCRs with those of their wild-type progenitors. Additionally, we performed molecular dynamics simulations to better understand the energetic mechanisms driving the affinity enhancements. These data demonstrate that supra-physiological binding affinities can be achieved without altering native TCR-pHLA binding modes via relatively subtle modifications to the interface contacts, often driven through the addition of buried hydrophobic residues. Individual energetic components of the TCR-pHLA interaction governing affinity enhancements were distinct and highly variable for each TCR, often resulting from additive, or knock-on, effects beyond the mutated residues. This comprehensive analysis of affinity-enhanced TCRs has important implications for the future rational design of engineered TCRs as efficacious and safe drugs for cancer treatment. Molecular Rules Underpinning Enhanced Affinity Binding of Human T Cell Receptors Engineered for Immunotherapy.,Crean RM, MacLachlan BJ, Madura F, Whalley T, Rizkallah PJ, Holland CJ, McMurran C, Harper S, Godkin A, Sewell AK, Pudney CR, van der Kamp MW, Cole DK Mol Ther Oncolytics. 2020 Jul 31;18:443-456. doi: 10.1016/j.omto.2020.07.008., eCollection 2020 Sep 25. PMID:32913893 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-2 microglobulin 3D structures MHC 3D structures MHC I 3D structures T-cell receptor 3D structures

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