6bga

2B4 I-Ek TCR-MHC complex with affinity-enhancing Velcro peptide

spinqualitylabelsall models 6bga, resolution 2.31Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6bga is a 5 chain structure with sequence from Mus musculus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.307Å Ligands: EDO, FUC, NAG, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function HA22_MOUSE Publication Abstract from PubMed T cell receptors (TCRs) bind to peptide-major histocompatibility complex (pMHC) with low affinity (Kd approximately muM), which is generally assumed to facilitate cross-reactive TCR "scanning" of ligands. To understand the relationship between TCR/pMHC affinity and cross-reactivity, we sought to engineer an additional weak interaction, termed "velcro," between the TCR and pMHC to probe the specificities of TCRs at relatively low and high affinities. This additional interaction was generated through an eight-amino acid peptide library covalently linked to the N terminus of the MHC-bound peptide. Velcro was selected through an affinity-based isolation and was subsequently shown to enhance the cognate TCR/pMHC affinity in a peptide-dependent manner by approximately 10-fold. This was sufficient to convert a nonstimulatory ultra-low-affinity ligand into a stimulatory ligand. An X-ray crystallographic structure revealed how velcro interacts with the TCR. To probe TCR cross-reactivity, we screened TCRs against yeast-displayed pMHC libraries with and without velcro, and found that the peptide cross-reactivity profiles of low-affinity (Kd > 100 muM) and high-affinity (Kd approximately muM) TCR/pMHC interactions are remarkably similar. The conservation of recognition of the TCR for pMHC across affinities reveals the nature of low-affinity ligands for which there are important biological functions and has implications for understanding the specificities of affinity-matured TCRs. Stress-testing the relationship between T cell receptor/peptide-MHC affinity and cross-reactivity using peptide velcro.,Gee MH, Sibener LV, Birnbaum ME, Jude KM, Yang X, Fernandes RA, Mendoza JL, Glassman CR, Garcia KC Proc Natl Acad Sci U S A. 2018 Jul 18. pii: 1802746115. doi:, 10.1073/pnas.1802746115. PMID:30021852 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also MHC 3D structures MHC I 3D structures T-cell receptor 3D structures

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