Predict the Strong Binding Ability Polypeptide of Human α-Enolase with the HLA-DRB1 * 0401

Abstract:

Human α-enolase (ENO1), an evolutionarily conserved and multifunctional protein, is a target self-antigen of rheumatoid arthritis (RA). Rheumatoid arthritis (RA) is genetically associated with MHC class II molecules, such as DRB1*0101, DRB1*0401 and DRB1*0404 allele. Among these DRB1 alleles, DRB1*0401 show the most correlation with RA. However, strong binding ability polypeptide of ENO1 with HLA-DRB1*0401 is still largely unknown. In this study, we used NetMHCII prediction method to predict the strong binding ability polypeptide with HLA-DRB1*0401. Among the 434 predicted fragment peptide, ENO1_129-141: PLYRHIADLAGNS showed strong binding with HLA-DR4 and peptide ENO1_281-293 KSFIKDYPVVSIE is the second candidate peptide. Based on these result, we choosed EON1_129-141 and EON1_281-293 polypeptides to do the molecular modeling, and used the molecular dynamics to optimize the three-dimensional structural model. The molecular dynamics results showed that ENO1_129-141: PLYRHIADLAGNS and ENO1_281-293: KSFIKDYPVVSIE have strong binding ability with HLA-DR4* 0401. In the shared epitope, both ENO1_129-141and ENO1_281-293 have the very near distance 3.15Å and 3.10Å with K71 of the β1 chain. The main-chain conformations of ENO1_129-141 sit more deeply with β1 chain. All together, results indicated that ENO1_129-141 and ENO1_281-293 bind strong with HLA-DR4 and would be potential T cell epitopes of human α-enolase that induced RA.

• Periodical: Applied Mechanics and Materials (Volumes 380-384)
• Pages: 4353-4358
• DOI: https://doi.org/10.4028/www.scientific.net/AMM.380-384.4353
• Online since: August 2013
• Authors: Rui Jie, Quan Zhou, Jin Song Wang, Yun He Liang, Ting Ting Liao, Jin Hui Yu, De Li Liu, Hui Geng
• Keywords: Epitope Predition, Human α-Enolase, Ligand Binding, Molecular Modeling

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