1ZHB

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

Summary for 1ZHB

• Entry DOI: 10.2210/pdb1zhb/pdb
• Related: 1JUF 1N5A 1S7U
• Descriptor: H-2 class I histocompatibility antigen, D-B alpha chain, Beta-2-microglobulin, 9-mer peptide from Dopamine beta-monooxygenase, ... (4 entities in total)
• Functional Keywords: mhc, tcr-crossreactivity, self-ligand, autoimmunity, immune system
• Biological source: Mus musculus (house mouse); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01899; Secreted: P01887; Soluble dopamine beta-hydroxylase: Cytoplasmic vesicle, secretory vesicle lumen . Cytoplasmic vesicle, secretory vesicle membrane ; Single-pass type II membrane protein : Q05754
• Total number of polymer chains: 12
• Total formula weight: 179381.17

Authors

Sandalova, T.,Michaelsson, J.,Harris, R.A.,Odeberg, J.,Schneider, G.,Karre, K.,Achour, A. (deposition date: 2005-04-25, release date: 2005-06-14, Last modification date: 2024-10-30)

Primary citation

Sandalova, T.,Michaelsson, J.,Harris, R.A.,Odeberg, J.,Schneider, G.,Karre, K.,Achour, A.
A structural basis for CD8+ T cell-dependent recognition of non-homologous peptide ligands: implications for molecular mimicry in autoreactivity
J.Biol.Chem., 280:27069-27075, 2005

PubMed Abstract: 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.

PubMed: 15845547
DOI: 10.1074/jbc.M500927200

Experimental method

X-RAY DIFFRACTION (2.7 Å)