Characterization of the novel HLA-A*24:191 allele and analysis of its MHC molecular modeling structure.
10.3760.cma.j.cn511374-20210705-00572
- Author:
Xiangmin NIE
1
;
Chuanfu ZHU
;
Haifeng ZHU
;
Yan LIU
;
Jingru SHAO
;
Wenben QIAO
Author Information
1. HLA Laboratory,Blood Center of Shandong Province, Jinan, Shandong 250014, China. niexmin@hotmail.com.
- Publication Type:Journal Article
- MeSH:
Alleles;
Amino Acid Sequence;
HLA-A Antigens;
Humans;
Peptides;
Protein Binding;
Protein Conformation
- From:
Chinese Journal of Medical Genetics
2022;39(5):505-509
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To characterize a novel HLA allele, A*24:191, its DNA sequence, MHC modeling structure, and the possible influence of the amino-acid residue variations on the molecule.
METHODS:The HLA sequence was determined by Luminex PCR-SSO and PCR-SBT. Its MHC molecular structure and the possible effects of the amino-acid residue variations were modeled and analyzed with Phyre2, RCSB PDB and HistoCheck software.
RESULTS:The PCR-SBT revealed the novel A*24:191 differs from A*24:02 in exon 2 at position 256, 265, 270 with G>C, G>C, A>T. The MHC molecular structure prediction showed that, compared with A*24:02, the 62nd residue of A*24:191 changed from the acidic E to a neutral Q, both with the side chain extending outside the α helix pointing forward the groove, (Risler's score, R=2), the 65th changed from the smaller neutral G extending inside the helix to a basic R with a long-chain extending upward outside the helix (R=52), and the 66th changed from the basic K to a neutral N both with a long side chain extending inside the groove (R=31). The above residues are located on the α helix of the α 1 domain which constituting the side wall of the peptide-binding groove. The DSS Score=3.85. From the surface image of the molecule, it can be clearly seen that the variations of the properties, sizes and configurations of the residues caused significant changes in the shape of the surface structure of the α helix.
CONCLUSION:It suggested that the residue variations are likely to change the peptide binding properties as well as the TCR and antibody binding characteristics of the molecule.
