Document Type : Original Article
Authors
1
Department of Medical Genetics, Shahid Sadoughi University of Medical Science, Yazd, Iran
2
Department of Biology, Science and Art University, Yazd, Iran
3
Immunology Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
4
Department of Biology Sciences, Shahid Rajaee Teacher Training University, Tehran, Iran
5
ATMP Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran
6
Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
7
Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
8
Biochemistry Department, Guilan University of Medical Sciences, Rasht, Iran
Abstract
Introduction: E. coli heme-utilization (ChuA) protein is an outer membrane protein, which has been shown as an amenable target for vaccine design studies. In the present study, we aimed to identify and characterize the most potent B and T cell epitopes of ChuA protein to unveil its most immunogenic regions.
Materials and Methods: In the present study, homology modeling was invoked to determine the three-dimensional (3D) structure of E. coli heme-utilization protein (ChuA). Thereafter, membrane topology, ligand binding site, surface accessibility, and clefts were assigned for ChuA, Linear and conformational B cell epitopes and T cell epitopes were predicted for ChuA. The 2D and 3D interaction plots between the most potent T cell epitopes and HLA-A020 and HLA-DRB0101 structures were drawn following the molecular docking analyses.
Results: Our results indicated that ChuA is heme ligand transporter protein, which forms a common beta-barrel structure. It is located in the membrane via 22 membrane-spanning regions. Residue–based pockets and clefts were identified on the ChuA protein. Immunological analyses revealed 9 highly potent B cell epitopes. Among predicted T cell epitopes 2 most potent epitopes were analyzed for HLA binding via molecular docking. The YSKQPGYG and FAAATTMSY epitopes showed stable interactions with HLA-A020 and HLA-DRB0101.
Conclusions: Our immunological, biochemical, and functional analysis highlighted the region of the ChuA protein, which harbors the highest immunogenic properties for vaccination purposes. Our strategy to employ 3D structure prediction and epitope prediction results could be deemed as an amenable approach for efficient vaccine design in various platforms.
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