2MHA

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

Summary for 2MHA

• Entry DOI: 10.2210/pdb2mha/pdb
• Descriptor: CLASS I HISTOCOMPATIBILITY ANTIGEN (H-2KB) (ALPHA CHAIN), BETA 2-MICROGLOBULIN, VIRAL OCTAPEPTIDE ARG-GLY-TYR-VAL-TYR-GLN-GLY-LEU (3 entities in total)
• Functional Keywords: histocompatibility antigen
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 6
• Total formula weight: 87502.19

Authors

Zhang, W.,Young, A.C.M.,Imarai, M.,Nathenson, S.G.,Sacchettini, J.C. (deposition date: 1993-07-21, release date: 1993-10-31, Last modification date: 2024-10-16)

Primary citation

Zhang, W.,Young, A.C.,Imarai, M.,Nathenson, S.G.,Sacchettini, J.C.
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.
Proc.Natl.Acad.Sci.USA, 89:8403-8407, 1992

PubMed Abstract: 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.

PubMed: 1325657
DOI: 10.1073/pnas.89.17.8403

Experimental method

X-RAY DIFFRACTION (2.5 Å)