The crystal structure of H-2D(b) complexed with a partial peptide epitope suggests a major histocompatibility complex class I assembly intermediate.
In the absence of bound peptide ligands, major histocompatibility complex (MHC) class I molecules are unstable. In an attempt to determine the minimum requirement for peptide-dependent MHC class I stabilization, we have used short synthetic peptides derived from the Sendai virus nucleoprotein epitope (residues 324-332, 1FAPGNYPAL9) to promote its folding in vitro of H-2D(b). We found that H-2D(b) can be stabilized by the pentapeptide 5NYPAL9, which is equivalent to the C-terminal portion of the optimal nonapeptide and includes both the P5 and P9 anchor residues. We have crystallized the complex of the H-2D(b) molecule with the pentamer and determined the structure to show how a quasi-stable MHC class I molecule can be formed by occupancy of a single binding pocket in the peptide-binding groove.
Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 4RU, United Kingdom.
Ann
A
Glithero
Jose
J
Tormo
Klaus
K
Doering
Mayumi
M
Kojima
E Yvonne
EY
Jones
Tim
T
Elliott
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000737:chemistry; D006183:H-2 Antigens / Q000737:chemistry*; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D008968:Molecular Conformation; D009698:Nucleoproteins / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D017433:Protein Structure, Secondary; D029082:Sendai virus / Q000378:metabolism
D000939:Epitopes; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D009698:Nucleoproteins; D010455:Peptides