8wul

Crystal structure of affinity enhanced TCR in complex with HLA-A*11:01 bound to KRAS-G12V peptide (VVGAVGVGK)

spinqualitylabelsall models 8wul, resolution 2.36Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8wul is a 20 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.36Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Neoantigens derived from somatic mutations in Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS), the most frequently mutated oncogene, represent promising targets for cancer immunotherapy. Recent research highlights the potential role of human leukocyte antigen (HLA) allele A*11:01 in presenting these altered KRAS variants to the immune system. In this study, we successfully generate and identify murine T-cell receptors (TCRs) that specifically recognize KRAS(8-16)(G12V) from three predicted high affinity peptides. By determining the structure of the tumor-specific 4TCR2 bound to KRAS(G12V)-HLA-A*11:01, we conduct structure-based design to create and evaluate TCR variants with markedly enhanced affinity, up to 15.8-fold. This high-affinity TCR mutant, which involved only two amino acid substitutions, display minimal conformational alterations while maintaining a high degree of specificity for the KRAS(G12V) peptide. Our research unveils the molecular mechanisms governing TCR recognition towards KRAS(G12V) neoantigen and yields a range of affinity-enhanced TCR mutants with significant potential for immunotherapy strategies targeting tumors harboring the KRAS(G12V) mutation. Identification and affinity enhancement of T-cell receptor targeting a KRAS(G12V) cancer neoantigen.,Zhang M, Xu W, Luo L, Guan F, Wang X, Zhu P, Zhang J, Zhou X, Wang F, Ye S Commun Biol. 2024 Apr 29;7(1):512. doi: 10.1038/s42003-024-06209-2. PMID:38684865 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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