Open AccessHigh‐resolution structure of HLA‐A*1101 in complex with SARS nucleocapsid peptide
Author(s) -
Blicher Thomas,
Kastrup Jette Sandholm,
Buus Søren,
Gajhede Michael
Publication year - 2005
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
ISSN - 1399-0047
DOI - 10.1107/s0907444905013090
Subject(s) - human leukocyte antigen , peptide , virology , computational biology , biology , genetics , antigen , biochemistry
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 Å resolution. The peptide is derived from the SARS‐CoV nucleocapsid protein positions 362–370 (SNP 362–370 ). 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 IC 50 values of 70 and 186 n M , 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–SNP 362–370 complex is very similar to other known structures of HLA‐A*1101 and HLA‐A*6801. The SNP 362–370 peptide is held in place by 17 hydrogen bonds to the α‐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.