Crystal Structure of H-2D[superscript b] Complexed with a Partial Peptide Epitope Suggests a Major Histocompatibility Complex Class I Assembly Intermediate

• Published in: The Journal of biological chemistry 2006-05, Vol.281 (18), p.12699-12704
• Main Authors: Glithero, Ann, Tormo, Jose, Doering, Klaus, Kojima, Mayumi, Jones, E. Yvonne, Elliott, Tim
• Format: Article
• Language: English
• Subjects: Animals; CHO Cells; Cricetinae; Crystallography, X-Ray; Epitopes - chemistry; H-2 Antigens - chemistry; Histocompatibility Antigen H-2D; Histocompatibility Antigens Class I - chemistry; Humans; Ligands; Molecular Conformation; Nucleoproteins - chemistry; Peptides - chemistry; Protein Structure, Secondary; Sendai virus - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M511683200

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[superscript b]. We found that H-2D[superscript 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[superscript 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.