7z50

Structure of the highly diabetogenic 4.1-T cell receptor targeting a hybrid insulin peptide bound to I-Ag7.

spinqualitylabelsall models 7z50, resolution 2.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7z50 is a 10 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.65Å Ligands: CL, EDO, NA, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed We recently provided evidence for promiscuous recognition of several different hybrid insulin peptides (HIPs) by the highly diabetogenic, I-A(g7)-restricted 4.1-T cell receptor (TCR). To understand the structural determinants of this phenomenon, we solved the structure of an agonistic HIP/I-A(g7) complex, both in isolation as well as bound to the 4.1-TCR. We find that HIP promiscuity of the 4.1-TCR is dictated, on the one hand, by an amino acid sequence pattern that ensures I-A(g7) binding and, on the other hand, by the presence of three acidic residues at positions P5, P7 and P8 that favor an optimal engagement by the 4.1-TCR's complementary determining regions. Surprisingly, comparison of the TCR-bound and unbound HIP/I-A(g7) structures reveals that 4.1-TCR binding triggers several novel and unique structural motions in both the I-A(g7) molecule and the peptide that are essential for docking. This observation indicates that the type 1 diabetes-associated I-A(g7) molecule is structurally malleable and that this plasticity allows the recognition of multiple peptides by individual TCRs that would otherwise be unable to do so. Structural plasticity in I-A(g7) links autoreactivity to hybrid insulin peptides in type I diabetes.,Erausquin E, Serra P, Parras D, Santamaria P, Lopez-Sagaseta J Front Immunol. 2022 Jul 28;13:924311. doi: 10.3389/fimmu.2022.924311. eCollection , 2022. PMID:35967292 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also T-cell receptor 3D structures

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