Dynamic characterization of HLA-B*44 Alleles: A comparative molecular dynamics simulation study |
| |
| Affiliation: | 1. Laboratory of Immunogenetics of Diseases, IdiPAZ Institute for Health Research, La Paz University Hospital, Madrid 28046, Spain;2. Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz University Hospital, Madrid 28046, Spain;3. Immunology Unit, La Paz University Hospital, Madrid 28046, Spain;4. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY 10065, USA;5. Howard Hughes Medical Institute, New York, NY 10065, USA;6. Immunology Division, Vall d''Hebron University Hospital, Barcelona 08035, Spain;7. Laboratory of Tumour Immunology, IdiPAZ Institute for Health Research, La Paz University Hospital, Madrid 28046, Spain;8. Laboratory of Image and Immunohistochemistry, IdiPAZ Institute for Health Research, La Paz University Hospital, Madrid 28046, Spain;9. Clinical Immunology Department, San Carlos Clinical Hospital, Madrid 28040, Spain;10. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris 75015, France;11. University Paris Descartes, Imagine Institute, Paris 75015, France;12. Paediatric Haematology-Immunology Unit, Necker Hospital for Sick Children, Paris 75015, France |
| |
| Abstract: | Human Leukocyte Antigens (HLA) are highly polymorphic proteins that play a key role in the immune system. HLA molecule is present on the cell membrane of antigen-presenting cells of the immune system and presents short peptides, originating from the proteins of invading pathogens or self-proteins, to the T-cell Receptor (TCR) molecule of the T-cells. In this study, peptide-binding characteristics of HLA-B*44:02, 44:03, 44:05 alleles bound to three nonameric peptides were studied using molecular dynamics simulations. Polymorphisms among these alleles (Asp116Tyr and Asp156Leu) result in major differences in the allele characteristics. While HLA-B*44:02 (Asp116, Asp156) and HLA-B*44:03 (Asp116, Leu156) depend on tapasin for efficient peptide loading, HLA-B*44:05 (Tyr116, Asp156) is tapasin independent. On the other hand, HLA-B*44:02 and HLA-B*44:03 mismatch is closely related to transplant rejection and acute-graft-versus-host disease. In order to understand the dynamic characteristics, the simulation trajectories were analyzed by applying Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuation (RMSF) calculations and hydrogen bonding analysis. Binding dynamics of the three HLA-B*44 alleles and peptide sequences are comparatively discussed. In general, peptide binding stability is found to depend on the peptide rather than the allele type for HLA-B*44 alleles. |
| |
| Keywords: | Molecular dynamics simulations HLA-B*44 alleles Tapasin dependency Peptide stability |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
