Structure of HLA-A*1101 in complex with a hepatitis B peptide homologue.
A high-resolution structure of the human MHC-I molecule HLA-A*1101 is presented in which it forms a complex with a sequence homologue of a peptide that occurs naturally in hepatitis B virus DNA polymerase. The sequence of the bound peptide is AIMPARFYPK, while that of the corresponding natural peptide is LIMPARFYPK. The peptide does not make efficient use of the middle E pocket for binding, which leads to a rather superficial and exposed binding mode for the central peptide residues. Despite this, the peptide binds with high affinity (IC50 of 31 nM).
Blicher
Thomas
T
Biostructural Research, Department of Medicinal Chemistry, The Danish University of Pharmaceutical Sciences, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Kastrup
Jette Sandholm
JS
Pedersen
Lars Østergaard
LØ
Buus
Søren
S
Gajhede
Michael
M
D000595:Amino Acid Sequence; D003460:Crystallization; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry*; D015234:HLA-A Antigens / Q000737:chemistry*; D059870:HLA-A11 Antigen; D006515:Hepatitis B virus / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D009842:Oligopeptides / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation
D015234:HLA-A Antigens; C515740:HLA-A*11:01 antigen; D059870:HLA-A11 Antigen; D009842:Oligopeptides; D010446:Peptide Fragments; C515741:alanyl-isoleucyl-methionyl-prolyl-alanyl-arginyl-phenylalanyl-tyrosyl-prolyl-lysine; D004259:DNA-Directed DNA Polymerase