5ihz | pdb_00005ihz

Crystal structure of anti-gliadin 1002-1E01 Fab fragment

spinqualitylabelsall models 5ihz, resolution 1.64Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ihz is a 8 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 5ig7, 5ijk, 5ifj Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The role of B cells and posttranslational modifications in pathogenesis of organ-specific immune diseases is increasingly envisioned but remains poorly understood, particularly in human disorders. In celiac disease, transglutaminase 2-modified (TG2-modified; deamidated) gluten peptides drive disease-specific T cell and B cell responses, and antibodies to deamidated gluten peptides are excellent diagnostic markers. Here, we substantiate by high-throughput sequencing of IGHV genes that antibodies to a disease-specific, deamidated, and immunodominant B cell epitope of gluten (PLQPEQPFP) have biased and stereotyped usage of IGHV3-23 and IGHV3-15 gene segments with modest somatic mutations. X-ray crystal structures of 2 prototype IGHV3-15/IGKV4-1 and IGHV3-23/IGLV4-69 antibodies reveal peptide interaction mainly via germline-encoded residues. In-depth mutational analysis showed restricted selection and substitution patterns at positions involved in antigen binding. While the IGHV3-15/IGKV4-1 antibody interacts with Glu5 and Gln6, the IGHV3-23/IGLV4-69 antibody interacts with Gln3, Pro4, Pro7, and Phe8 - residues involved in substrate recognition by TG2. Hence, both antibodies, despite different interaction with the epitope, recognize signatures of TG2 processing that facilitates B cell presentation of deamidated gluten peptides to T cells, thereby providing a molecular framework for the generation of these clinically important antibodies. The study provides essential insight into the pathogenic mechanism of celiac disease. Stereotyped antibody responses target posttranslationally modified gluten in celiac disease.,Snir O, Chen X, Gidoni M, du Pre MF, Zhao Y, Steinsbo O, Lundin KE, Yaari G, Sollid LM JCI Insight. 2017 Sep 7;2(17). pii: 93961. doi: 10.1172/jci.insight.93961. PMID:28878138 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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