1rk0
From Proteopedia
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Mhc Class I H-2Kb Heavy Chain Complexed With beta-2 Microglobulin and Herpes Simplex Virus Glycoprotein B peptide
Overview
Major histocompatibility complex (MHC) class I variants H-2K(b) and H-2K(bm8) differ primarily in the B pocket of the peptide-binding groove, which serves to sequester the P2 secondary anchor residue. This polymorphism determines resistance to lethal herpes simplex virus (HSV-1) infection by modulating T cell responses to the immunodominant glycoprotein B(498-505) epitope, HSV8. We studied the molecular basis of these effects and confirmed that T cell receptors raised against K(b)-HSV8 cannot recognize H-2K(bm8)-HSV8. However, substitution of Ser(P2) to Glu(P2) (peptide H2E) reversed T cell receptor (TCR) recognition; H-2K(bm8)-H2E was recognized whereas H-2K(b)-H2E was not. Insight into the structural basis of this discrimination was obtained by determining the crystal structures of all four MHC class I molecules in complex with bound peptide (pMHCs). Surprisingly, we find no concerted pMHC surface differences that can explain the differential TCR recognition. However, a correlation is apparent between the recognition data and the underlying peptide-binding groove chemistry of the B pocket, revealing that secondary anchor residues can profoundly affect TCR engagement through mechanisms distinct from the alteration of the resting state conformation of the pMHC surface.
About this Structure
1RK0 is a Protein complex structure of sequences from Mus musculus with as ligand. Full crystallographic information is available from OCA.
Reference
Structural basis for the restoration of TCR recognition of an MHC allelic variant by peptide secondary anchor substitution., Miley MJ, Messaoudi I, Metzner BM, Wu Y, Nikolich-Zugich J, Fremont DH, J Exp Med. 2004 Dec 6;200(11):1445-54. Epub 2004 Nov 22. PMID:15557346
Page seeded by OCA on Thu Feb 21 14:51:43 2008
Categories: Mus musculus | Protein complex | Fremont, D H. | Messaoudi, I. | Miley, M J. | Nikolich-Zugich, J. | NDG | Class i | Herpes | Mhc | Peptide | Tcr | Virus