Decamer-like conformation of a nona-peptide bound to HLA-B*3501 due to non-standard positioning of the C terminus.
The N and C termini of peptides presented by major histocompatibility complex (MHC) class I molecules are held within the peptide binding groove by a network of hydrogen bonds to conserved MHC residues. However, the published structure of the human allele HLA-B*3501 complexed with the nef octa-peptide VPLRPMTY, revealed non-standard positioning for both peptide termini. To investigate whether these deviations are indeed related to the length of the nef-peptide, we have determined the structure of HLA-B*3501 presenting a nona-peptide to 2.5 A resolution. A comparison of HLA-B*3501/peptide complexes with structures of other HLA molecules exhibits allele-specific properties of HLA-B*3501, as well as peptide-induced structural changes. Independent of the length of the bound peptide, HLA-B*3501 positions the peptide C terminus significantly closer to the alpha1-helix and nearer to the A pocket than observed for other HLA class I/peptide complexes. This reorientation is accompanied by a shift within the N-terminal part of the alpha2-helix towards the middle of the binding groove. Due to the short distance between the N and C termini, the nona-peptide is compressed and forced to zig-zag vertically within the binding groove. Its conformation rather resembles that of a deca-peptide than of other nona-peptides bound to class I molecules. Superposition of both HLA-B*3501/peptide complexes additionally reveals a significant, peptide-dependent deviation between the N-terminal parts of the alpha1-helices which might be due to different positioning of the peptide N termini. Taken together, these data illustrate the strong interdependence between the HLA class I molecule and the bound peptide.
Menssen
R
R
Institut für Immungenetik Universitätsklinikum Charité, Humboldt-Universität zu Berlin, Spandauer Damm 130, Berlin, D-14050, Germany.
Orth
P
P
Ziegler
A
A
Saenger
W
W
D000483:Alleles; D000595:Amino Acid Sequence; D001665:Binding Sites; D019309:Epstein-Barr Virus Nuclear Antigens / Q000737:chemistry* / Q000276:immunology; D015797:HLA-B35 Antigen / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000276:immunology; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D019309:Epstein-Barr Virus Nuclear Antigens; D015797:HLA-B35 Antigen; D010455:Peptides