Crystal Structures of Two Viral Peptides in Complex with Murine MHC Class I H-2K ^b

TLDR

X‑ray crystallography at 2.3–2.5 Å resolved H‑2K b complexes with VSV‑8 and SEV‑9 peptides. The structures show that H‑2K b closely resembles human HLA class I, with peptides adopting extended conformations and a central bulge that preserves terminal contacts, side‑chain interactions that explain peptide diversity, and peptide‑induced conformational changes likely important for T‑cell recognition.

Abstract

The x-ray structures of a murine MHC class I molecule (H-2K b ) were determined in complex with two different viral peptides, derived from the vesicular stomatitis virus nucleoprotein (52-59), VSV-8, and the Sendai virus nucleoprotein (324-332), SEV-9. The H-2K b complexes were refined at 2.3 Å for VSV-8 and 2.5 Å for SEV-9. The structure of H-2K b exhibits a high degree of similarity with human HLA class I, although the individual domains can have slightly altered dispositions. Both peptides bind in extended conformations with most of their surfaces buried in the H-2K b binding groove. The nonamer peptide maintains the same amino- and carboxyl-terminal interactions as the octamer primarily by the insertion of a bulge in the center of an otherwise β conformation. Most of the specific interactions are between side-chain atoms of H-2K b and main-chain atoms of peptide. This binding scheme accounts in large part for the enormous diversity of peptide sequences that bind with high affinity to class I molecules. Small but significant conformational changes in H-2K b are associated with peptide binding, and these synergistic movements may be an integral part of the T cell receptor recognition process.