2a83
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Crystal structure of hla-b*2705 complexed with the glucagon receptor (gr) peptide (residues 412-420)
OverviewOverview
An interesting property of certain peptides presented by major, histocompatibility complex (MHC) molecules is their acquisition of a dual, binding mode within the peptide binding groove. Using x-ray, crystallography at 1.4 A resolution, we show here that the glucagon, receptor-derived self-peptide pGR ((412)RRRWHRWRL(420)) is presented by, the disease-associated human MHC class I subtype HLA-B*2705 in a dual, conformation as well, with the middle of the peptide bent toward the floor, of the peptide binding groove of the molecule in both binding modes. The, conformations of pGR are compared here with those of another self-peptide, (pVIPR, RRKWRRWHL) that is also displayed in two binding modes by, HLA-B*2705 antigens and with that of the viral peptide pLMP2 (RRRWRRLTV)., Conserved structural features suggest that the N-terminal halves of the, peptides are crucial in allowing cytotoxic T lymphocyte (CTL), cross-reactivity. In addition, an analysis of T cell receptors (TCRs) from, pGR- or pVIPR-directed, HLA-B27-restricted CTL clones demonstrates that, TCR from distinct clones but with comparable reactivity may share, CDR3alpha but not CDR3beta regions. Therefore, the cross-reactivity of, these CTLs depends on TCR-CDR3alpha, is modulated by TCR-CDR3beta, sequences, and is ultimately a consequence of the conformational, dimorphism that characterizes binding of the self-peptides to HLA-B*2705., These results lend support to the concept that conformational dimorphisms, of MHC class I-bound peptides might be connected with the occurrence of, self-reactive CTL.
DiseaseDisease
Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[142830], Hypoproteinemia, hypercatabolic OMIM:[109700], Spondyloarthropathy, susceptibility to, 1 OMIM:[142830], Stevens-Johnson syndrome, carbamazepine-induced, susceptibility to OMIM:[142830]
About this StructureAbout this Structure
2A83 is a Protein complex structure of sequences from Homo sapiens with NA and GOL as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Conformational dimorphism of self-peptides and molecular mimicry in a disease-associated HLA-B27 subtype., Ruckert C, Fiorillo MT, Loll B, Moretti R, Biesiadka J, Saenger W, Ziegler A, Sorrentino R, Uchanska-Ziegler B, J Biol Chem. 2006 Jan 27;281(4):2306-16. Epub 2005 Oct 12. PMID:16221670
Page seeded by OCA on Mon Nov 12 20:47:13 2007