4z76

Weak TCR binding to an unstable insulin epitope drives type 1 diabetes

spinqualitylabelsall models 4z76, resolution 1.88Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4z76 is a 6 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 1.88Å Ligands: EDO, GOL, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function HA1D_MOUSE Involved in the presentation of foreign antigens to the immune system. Publication Abstract from PubMed The NOD mouse model of type 1 diabetes (T1D) continues to be an important tool for delineating the role of T-cell-mediated destruction of pancreatic beta-cells. However, little is known about the molecular mechanisms that enable this disease pathway. We show that insulin reactivity by a CD8+ T-cell clone known to induce T1D is characterised by weak T cell antigen receptor (TCR) binding to a relatively unstable peptide-major histocompatibility complex (pMHC). The structure of the native 9-mer and 10-mer insulin epitopes demonstrated that peptide residues 7 and 8 form a prominent solvent exposed bulge that could potentially be the main focus of TCR binding. The C-terminus of the peptide governed pMHC stability. Unexpectedly, we further demonstrate a novel mode of flexible peptide presentation in which the MHC peptide-binding groove is able to 'open the back door' to accommodate extra C-terminal peptide residues. Distortion of the MHC class I binding groove to accommodate an insulin-derived 10-mer peptide.,Motozono C, Pearson JA, De Leenheer E, Rizkallah PJ, Beck K, Trimby A, Sewell AK, Wong FS, Cole DK J Biol Chem. 2015 Jun 17. pii: jbc.M114.622522. PMID:26085090 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-2 microglobulin 3D structures

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