5jwe | pdb_00005jwe
Crystal structure of H-2Db in complex with the LCMV-derived GP92-101 peptide
Structural highlights
Function[HA11_MOUSE] Involved in the presentation of foreign antigens to the immune system. [GLYC_LYCVA] Stable signal peptide (SSP) is cleaved but is apparently retained as the third component of the GP complex. The SSP is required for efficient glycoprotein expression, post-translational cleavage of GP1 and GP2, glycoprotein transport to the cell plasma membrane, formation of infectious virus particles, and acid pH-dependent glycoprotein-mediated cell fusion.[1] Glycoprotein G1 mediates virus attachment to host receptor alpha-dystroglycan DAG1. This attachment induces virion internalization predominantly through clathrin- and caveolin-independent endocytosis.[2] Glycoprotein G2 is a class I viral fusion protein, that directs fusion of viral and host endosomal membranes, leading to delivery of the nucleocapsid into the cytoplasm. Membrane fusion is mediated by irreversable conformational changes induced upon acidification in the endosome.[3] [B2MG_MOUSE] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. Publication Abstract from PubMedPost-translational modifications significantly broaden the epitope repertoire for major histocompatibility class I complexes (MHC-I) and may allow viruses to escape immune recognition. Lymphocytic choriomeningitis virus (LCMV) infection of H-2b mice generates CD8+ CTL responses directed towards several MHC-I-restricted epitopes including the peptides GP92 (CSANNSHHYI) and GP392 (WLVTNGSYL), both with a N-glycosylation site. Interestingly, glycosylation has different effects on the immunogenicity and association capacity of these two epitopes to H-2Db. To assess the structural bases underlying these functional results, we determined the crystal structures of H-2Db in complex with GP92 (CSANNSHHYI) and GP392 (WLVTNGSYL) to 2.4 and 2.5 A resolution, respectively. The structures reveal that while glycosylation of GP392 most probably impairs binding, the glycosylation of the asparagine residue in GP92, which protrudes towards the solvent, possibly allows for immune escape and/or forms a neo-epitope that may select for a different set of CD8 T cells. Altogether, the presented results provide a structural platform underlying the effects of post-translational modifications on epitope binding and/or immunogenicity, resulting in viral immune escape. Crystal structures of H-2Db in complex with the LCMV-derived peptides GP92 and GP392 explain pleiotropic effects of glycosylation on antigen presentation and immunogenicity.,Hafstrand I, Badia-Martinez D, Josey BJ, Norstrom M, Buratto J, Pellegrino S, Duru AD, Sandalova T, Achour A PLoS One. 2017 Dec 18;12(12):e0189584. doi: 10.1371/journal.pone.0189584., eCollection 2017. PMID:29253009[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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