High-resolution structure of HLA-A*1101 in complex with SARS nucleocapsid peptide.
The structure of the human MHC-I molecule HLA-A*1101 in complex with a nonameric peptide (KTFPPTEPK) has been determined by X-ray crystallography to 1.45 A resolution. The peptide is derived from the SARS-CoV nucleocapsid protein positions 362-370 (SNP362-370). It is conserved in all known isolates of SARS-CoV and has been verified by in vitro peptide-binding studies to be a good to intermediate binder to HLA-A*0301 and HLA-A*1101, with IC50 values of 70 and 186 nM, respectively [Sylvester-Hvid et al. (2004), Tissue Antigens, 63, 395-400]. In terms of the residues lining the peptide-binding groove, the HLA-A*1101-SNP362-370 complex is very similar to other known structures of HLA-A*1101 and HLA-A*6801. The SNP362-370 peptide is held in place by 17 hydrogen bonds to the alpha-chain residues and by nine water molecules which are also tightly bound in the peptide-binding groove. Thr6 of the peptide (Thr6p) does not make efficient use of the middle (E) pocket. For vaccine development, there seems to be a potential for optimization targeted at this position. All residues except Thr2p and Lys9p are accessible for T-cell recognition.
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
Buus
Søren
S
Gajhede
Michael
M
D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray / Q000379:methods; D015234:HLA-A Antigens / Q000737:chemistry*; D019590:Nucleocapsid Proteins / Q000737:chemistry*; D017433:Protein Structure, Secondary; D045473:Severe acute respiratory syndrome-related coronavirus / Q000737:chemistry*
D015234:HLA-A Antigens; D019590:Nucleocapsid Proteins