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1zhb
From Proteopedia
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Crystal Structure Of The Murine Class I Major Histocompatibility Complex Of H-2Db, B2-Microglobulin, and a 9-Residue Peptide Derived from rat dopamine beta-monooxigenase
Overview
Molecular mimicry of self-epitopes by viral antigens is one possible, pathogenic mechanism underlying induction of autoimmunity. A self-epitope, mDBM, derived from mouse dopamine beta-mono-oxygenase (KALYDYAPI) sharing, 44% sequence identity with the lymphocytic choriomeningitis virus-derived, immunodominant epitope gp33 (KAVYNFATC/M), has previously been identified, as a cross-reactive self-ligand, presentation of which results in, autoimmunity. A rat peptide homologue, rDBM (KALYNYAPI, 56% identity to, gp33), which displayed similar properties to mDBM, has also been, identified. We herein report the crystal structure of H-2Db.rDBM and a, comparison with the crystal structures of the cross-reactive H-2Db.gp33, and non-cross-reactive H-2Db.gp33 (V3L) escape variant (KALYNFATM, 88%, identity to gp33). Despite the large sequence disparity, rDBM and gp33, peptides are presented in nearly identical manners by H-2Db, with a, striking juxtaposition of the central sections of both peptides from, residues p3 to p7. The structural similarity provides H-2Db in complex, with either a virus-derived or a dopamine beta-mono-oxygenase-derived, peptide with a shared antigenic identity that conserves the positioning of, the heavy chain and peptide residues that interact with the T cell, receptor (TCR). This stands in contrast to the structure of H-2Db.gp33, (V3L), in which a single conserved mutation, also present in rDBM, induces, large movements of both the peptide backbone and the side chains that, interact with the TCR. The TCR-interacting surfaces of the H-2Db.rDBM and, H-2Db.gp33 major histocompatibility complexes are very similar with regard, to shape, topology, and charge distribution, providing a structural basis, for CD8 T cell activation by molecular mimicry and potential subsequent, development of autoreactivity.
About this Structure
1ZHB is a Protein complex structure of sequences from Mus musculus. Active as Dopamine beta-monooxygenase, with EC number 1.14.17.1 Full crystallographic information is available from OCA.
Reference
A structural basis for CD8+ T cell-dependent recognition of non-homologous peptide ligands: implications for molecular mimicry in autoreactivity., Sandalova T, Michaelsson J, Harris RA, Odeberg J, Schneider G, Karre K, Achour A, J Biol Chem. 2005 Jul 22;280(29):27069-75. Epub 2005 Apr 21. PMID:15845547
Page seeded by OCA on Wed Nov 21 07:27:18 2007
