2mha

From Proteopedia

---

Revision as of 10:37, 21 November 2007

proteopedia linkproteopedia link

spinqualitylabelsall models 2mha, resolution 2.5Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CRYSTAL STRUCTURE OF THE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I H-2KB MOLECULE CONTAINING A SINGLE VIRAL PEPTIDE: IMPLICATIONS FOR PEPTIDE BINDING AND T-CELL RECEPTOR RECOGNITION

Overview

To study the structure of a homogenous major histocompatibility complex, (MHC) class I molecule containing a single bound peptide, a complex of, recombinant mouse H-2Kb, beta 2-microglobulin (beta 2m), and a fragment of, the vesicular stomatitis virus (VSV) nuclear capsid protein, VSV-(N52-59), octapeptide (Arg-Gly-Tyr-Val-Tyr-Gln-Gly-Leu), was prepared by exploiting, a high-yield bacterial expression system and in vitro cocomplex formation., The structure of mouse H-2Kb revealed its similarity to three human class, I HLA molecules, consistent with the high primary sequence homology and, common function of these peptide-presenting molecules. Electron density, was located in the peptide-binding groove, to which a single peptide in a, unique conformation was unambiguously fit. The peptide extends the length, of the groove, parallel to the alpha-helices, and assumes an extended, mostly beta-strand conformation. The peptide is constrained within the, groove by hydrogen bonding of its main-chain atoms and by contacts of its, side chains with the H-2Kb molecule. The amino-terminal nitrogen atom of, the peptide forms a hydrogen bond with the hydroxyl group of Tyr-171 of, H-2Kb at one end of the groove, while the carboxyl-terminal oxygen forms a, hydrogen bond with the hydroxyl group of Tyr-84 at the other end. Since, the amino acids at both ends are conserved among human and mouse MHC, molecules, this anchoring of each end of the peptide appears to be a, general feature of peptide-MHC class I molecule binding and imposes, restrictions on its length. The side chains of residues Tyr-3, Tyr-5, and, Leu-8 of the VSV octapeptide fit into the interior of the H-2Kb molecule, with no appreciable surface exposure, a finding in support of previous, biological studies that showed the importance of these residues for, binding. Thus, the basis for binding of specific peptide sequences to the, MHC class I molecule is the steric restriction imposed on the peptide side, chains by the architecture of the floor and sides of the groove. The side, chains of Arg-1, Val-4, and Gln-6 and the main-chain of Gly-7 of the, octapeptide are exposed on the surface of the complex, thus confirming, their availability for T-cell receptor contact, as previously demonstrated, by T-cell recognition experiments.

About this Structure

2MHA is a Protein complex structure of sequences from Mus musculus and Vesicular stomatitis virus. Full crystallographic information is available from OCA.

Reference

Crystal structure of the major histocompatibility complex class I H-2Kb molecule containing a single viral peptide: implications for peptide binding and T-cell receptor recognition., Zhang W, Young AC, Imarai M, Nathenson SG, Sacchettini JC, Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8403-7. PMID:1325657

Page seeded by OCA on Wed Nov 21 12:44:51 2007