Agricultural and Biological Sciences Journal
Articles Information
Agricultural and Biological Sciences Journal, Vol.5, No.2, Jun. 2019, Pub. Date: May 28, 2019
Prediction and Analysis of Key Sites for Hepatitis B Antigen-antibody Interactions: Computational Simulation
Pages: 50-59 Views: 55 Downloads: 49
[01] Linsong Yang, Biomedicine Laboratory, School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou, China.
[02] Weiwei Ji, Biomedicine Laboratory, School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou, China.
[03] Hui Zhong, Biomedicine Laboratory, School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou, China.
[04] Fang Wang, Biomedicine Laboratory, School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou, China.
The phenomenon of immune escape and diagnostic escape caused by mutations of "a" determinant region is becoming more and more frequent. It is now well established that the preS2 region has the highly immunogenicity. However, the mechanism of the preS2 as an antigen epitope interacting with antibody have been poorly investigated. The present study simulation analyzed the structure and immunogenic activity of the preS2 and predicted key sites for antigen-antibody interactions. Three-dimensional structure of the HBV envelope Large (preS1+preS2+S) protein was predicted and optimized using several web tools. Then we evaluated the quality of the 3D structure. After that we used protein-protein Docking module in BioLuminate software to analyze the docking of antigen antibodies and Residue Scanning in Maestro BioLuminate was used to replace some residues on the antigen by Alanine, respectively. Meanwhile, the CHARMm force field in DS software was used for molecular dynamics simulation analysis of composite surface interaction. MET120, GLN121, TRP122, ASN123, PHE127 and LEU132 on preS2 are key sites for interaction with antibodies. When these sites were replaced with alanine cause a considerable reduction in the tightness and stability of protein complexes. And these mutation in the preS2, leading to a reduced binging ability to its monoclonal antibody, F124. These data will be beneficial for designing more advanced antibodies. It has practical value in guiding experimenters to rationally design and analyze protein-protein interactions. The results of this study may assist in the design or development of more effective hepatitis B vaccines.
PreS2 Antigen, Residue Scanning, Computational Simulation, HBV Vaccines, Homology Modeling
[01] Verma, R, Khanna, P, Prinja, S, Rajput, M, Chawla, S, and Bairwa, M, (2011). Hepatitis B Vaccine in national immunization schedule: A preventive step in India. Human Vaccines. vol 7, pp. 1387-1388.
[02] Lamontagne, R. J, Bagga, S, Bouchard, and M. J, (2016). Hepatitis B virus molecular biology and pathogenesis. Hepatoma Research. vol 2, pp. 163-186.
[03] Ou, J. H. (1997). Molecular biology of hepatitis B virus e antigen. Journal of Gastroenterology and Hepatology. vol 12, pp. 178-187.
[04] Wei, Y, Neuveut, C, Tiollais, P, and Buendia, M. A, (2018). Molecular biology of the hepatitis B virus and role of the X gene. Pathologie Biologie. vol 58, pp. 267-272.
[05] Wu, C. C, Chen, Y. S, Cao, L, X. W, and Lu, M. J, (2018). Hepatitis B virus infection: defective surface antigen expression and pathogenesis. World Journal of Gastroenterology. vol 24, pp. 3488-3499.
[06] Peterson, D. L, Roberts, I. M, and Vyas, G. N, (1997). Partial amino acid sequence of two major component polypeptides of hepatitis B surface antigen. Proceedings of the National Academy of Sciences of the United States of America. vol 74, pp. 1530-1534.
[07] Carman, W. F, Zanetti, A. R, Karayiannis, P, Waters, J, Manzillo, G, Tanzi, E, Zuckerman, A. J, and Thomas, H. C, (1990). Vaccine-induced escape mutant of hepatitis B virus. The Lancet. vol 336, pp. 325-329.
[08] Hadiji-Abbes, N, Borchani-Chabchoub, I, Triki, H, Ellouz, R, Gargouri, A, and Mokdad-Gargouri, R, (2009). Expression of HBsAg and preS2-S protein in different yeast based system: a comparative analysis. Protein Expression and Purification. vol 66, pp. 131-137.
[09] Langley, K. E, Egan, K. M, Barendt, J. M, Parker, C. G, and Bitter, G. A, (1998). Characterization of purified hepatitis B surface antigen containing pre-S (2) epitopes expressed in Saccharomyces cerevisiae. Gene. vol 67, pp. 229-245.
[10] Oess, S, Hildt, E, (2000). Novel cell permeable motif derived from the PreS2-domain of hepatitis-B virus surface antigens. Gene Therapy. vol 7 pp. 750-758.
[11] Liu, P, Zhang, H, Liang, X, Ma, H, Luan, F, Wang, B, Bai, F, Gao, L, and Ma, C, (2015). HBV preS2 promotes the expression of TAZ via miRNA-338-3p to enhance the tumorigenesis of hepatocellular carcinoma. Oncotarget. vol 6, pp. 29048-29059.
[12] Zhang, X, Gao, L, Liang, X, Guo, M, Wang, R, Pan, Y, Liu, P, Zhang, F, Guo, C, Zhu, F, Qu, C, and Ma, C, (2015). HBV preS2 transactivates FOXP3 expression in malignant hepatocytes. Liver International. vol 35, pp. 1087-1094.
[13] Luan, F, Liu, B, Zhang, J, Cheng, S, Zhang, B, and Wang, Y, (2017). Correlation between HBV protein preS2 and tumor markers of hepatocellular carcinoma. Pathology - Research and Practice. vol 213, pp. 1037-1042.
[14] Milich, D. R, Thornton, G. B, Neurath, A. R, Kent, S. B, Michel, M. L, Tiollais, P, and Chisari, F. V, (1985). Enhanced immunogenicity of the pre-S region of hepatitis B surface antigen. Science. vol 228, pp. 1195–1199.
[15] Natasha, M, (2008). Molecular Embodiments and the Body-Work of Modeling in Protein Crystallography. Social Studies of Science. vol 38, pp. 163-199.
[16] Remmert, M, Biegert, A, Hauser, A, and Söding, J, (2012). HHblits: lightning-fast iterative protein sequence searching by HMM-HMM alignment. Nature methods. vol 9, pp. 173-175.
[17] Jones, D. T, (1999). Protein secondary structure prediction based on position-specific scoring matrices. Journal of Molecular Biology. vol 292, pp. 195-202.
[18] Altschul, S. F, (1997). Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. vol 25, pp. 3389-3402.
[19] Jefferys, B. R, Kelley, L. A, and Sternberg, M. J, (2010). Protein folding requires crowd control in a simulated cell. Journal of Molecular Biology. vol 397, pp. 1329-1338.
[20] Kelley, L. A, Mezulis, S, Yates, C. M, Wass, M. N, Sternberg, M. J, (2015). The Phyre2 web portal for protein modeling, prediction and analysis. Nature Protocols. vol 10, pp. 845-858.
[21] Xu, D, Zhang, Y, (2011). Improving the Physical Realism and Structural Accuracy of Protein Models by a Two-Step Atomic-Level Energy Minimization. Biophysical Journal. vol 101, pp. 2525-2534.
[22] Laskowski, R. A, Macarthur, M. W, Moss, D. S, and Thornton, J. M, (1993). PROCHECK a program to check the stereochemical quality of protein structures. Journal of Applied Crystallography. vol 26, pp. 283-291.
[23] Colovos, C, Yeates, T. O, (1993). Verification of protein structures: patterns of nonbonded atomic interactions. Protein Science. vol 2, pp. 1511-1519.
[24] Bowie, J, Luthy, R, and Eisenberg, D, (1991). A method to identify protein sequences that fold into a known three-dimensional structure. Science. vol 253, pp. 164-170.
[25] Saul, F. A, Normand, V. L, Passafiume, M, Riottot, M. M, and Bentley, (2000). Structure of the Fab fragment from F124, a monoclonal antibody specific for hepatitis B surface antigen. Acta Crystallographica Section D Biological Crystallography. vol 56, pp. 945-951.
[26] Comeau, S. R, Gatchell, D. W, Vajda, S, and Camacho, C. J (2004). ClusPro: a fully automated algorithm for protein–protein docking. Nucleic Acids Research. vol 32, pp. W96–W99.
[27] Kozakov, D, Brenke, R, Comeau, S, and Vajda, S, (2006). IPER: an FFT-based protein docking program with pairwise potentials. Proteins. vol 65, pp. 392-406.
[28] Wodak, S. J, and Janin, J, (1978). Computer analysis of protein-protein interaction. Journal of Molecular Biology. vol 124, pp. 323-342.
[29] Wang, L, Berne, B. J, and Friesner, R. A, (2012). On achieving high accuracy and reliability in the calculation of relative protein–ligand binding affinities. Proceedings of the National Academy of Sciences of the United States of America. vol 109, pp. 1937-1942.
[30] Tovchigrechko, A, and Vakser, I. A, (2001). How Common is the Funnel-Like Energy Landscape in Protein-Protein Interactions?. Protein Science. vol 10, pp. 1572-1583.
[31] Vakser, I. A, (2015). Low-resolution docking: prediction of complexes for underdetermined structures. Biopolymers. vol 39, pp. 455-464.
[32] Kulandaisamy, A., Lathi, V, Viswapoorani, K, Yugandhar, K, and Gromiha, M. M, (2016). Important amino acid residues involved in folding and binding of protein-protein complexes. International Journal of Biological Macromolecules. vol 94, pp. 438-444.
[33] Durell, S. R, and Ben-Naim, A, (2017). Hydrophobic-Hydrophilic Forces in Protein Folding. Biopolymers. 107 (8).
[34] Gates, Z. P, Baxa, M. C, Yu, W, Riback, J. A, Li, H, Roux, B, Kent, S. B, and Sosnick, T. R, (2017). Perplexing cooperative folding and stability of a low-sequence complexity, polyproline 2 protein lacking a hydrophobic core. Proceedings of the National Academy of Sciences. vol 114, pp. 2241-2246.
[35] Pace, C. N, Shirley, B. A, McNutt, M, and Gajiwala, K, (1996). Forces contributing to the conformational stability of proteins. Faseb Journal Official Publication of the Federation of American Societies for Experimental Biology. vol 10, pp. 75-83.
[36] Miu, L, Bogatyreva, N. S, and Galzitskaia, O. V, (2008). Radius of gyration is indicator of Radius of protein structure compactness. Molecular Biology. vol 42, pp. 701–706.
[37] Lee, K. M, Kim, Y. S, Ko, Y. Y, Yoo, B. M, Lee KJ, Kim, J. H, Hahm, K. B, and Cho, S. W, (2001). Emergence of vaccine-induced escape mutant of hepatitis B virus with multiple surface gene mutations in a Korean child. Journal of Korean Medical Science. vol 16, pp. 359-362.
[38] Bahn, A, Gerner, P, Martiné, U, Bortolotti, F, and Wirth, S, (1997). Detection of different viral strains of hepatitis B virus in chronically infected children after seroconversion from HBsAg to anti-HBs indicating viral persistence. Journal of Hepatology. vol 27, pp. 973–978.
[39] Ghany, M. G, Ayola, B, Villamil, F. G, Gish, R. G, Rojter, S, Vierling, J. M, and Lok, A. S, (1998). Hepatitis B virus S mutants in liver transplant recipients who were reinfected despite hepatitis B immune globulin prophylaxis. Hepatology. vol 27, pp. 213–222.
[40] Protzer-Knolle, U, Naumann, U, Bartenschlager, R, Berg, T, Hopf, U, Meyer, zum, Büschenfelde, K. H, Neuhaus, P, and Gerken, G, (1998). Hepatitis B virus with antigenically altered hepatitis B surface antigen is selected by high-dose hepatitis B immune globulin after liver transplantation. Hepatology. vol 27, pp. 254-263.
[41] Waters, J. A, (1992). Loss of the common “A” determinant of hepatitis B surface antigen by a vaccine-induced escape mutant. Journal of Clinical Investigation. vol 90, pp. 2543–2547.
[42] Yamada T, Iwabuki H, Kanno T, Tanaka H, Kawai T, Fukuda H, Kondo A, Seno M, Tanizawa K, and Kuroda S, (2001). Physicochemical and immunological characterization of hepatitis B virus envelope particles exclusively consisting of the entire L (pre-S1+pre-S2+S) protein. Vaccine. vol 19, pp. 3154-3163.
[43] Gerlich, W. H, Deepen, R, Heermann, K. H, Krone, B, Lu, X. Y, Seifer, M, and Thomssen, R, (1990). Protective potential of hepatitis B virus antigens other than the S gene protein. Vaccine. vol 8, pp. S63-S68.
[44] Kuroda, S, Fujisawa, Y, Iino, S, Akahane, Y, and Suzuki, H, (1991). Induction of protection level of anti-pres2 antibodies in humans immunized with a novel hepatitis B vaccine consisting of M (preS2 þ S) protein particles (a third generation vaccine). Vaccine. vol 9, pp. 163–169.
[45] Ponsel, D, and Bruss, V, (2003). Mapping of Amino Acid Side Chains on the Surface of Hepatitis B Virus Capsids Required for Envelopment and Virion Formation. Journal of Virology. vol 77, pp. 416-422.
[46] El-Mowafy, M, Elgaml, A, El-Mesery, M, and Elegezy, M, (2017). Molecular analysis of Hepatitis B virus sub-genotypes and incidence of preS1/preS2 region mutations in HBV-infected Egyptian patients from Mansoura. Journal of Medical Virology. vol 89, pp. 1559-1566.
[47] Chen, J, Lu, Z, Sakon, J, and Stites, W. E, (2000). Increasing the thermostability of staphylococcal nuclease: implications for the origin of protein thermostability. Journal of Molecular Biology. vol 303, pp. 125–130.
[48] Hennig, M, Darimont, B, Sterner, R, Kirschner, K, Jansonius, and J. N, (1995). 2.0 A structure of indole-3-glycerol phosphate synthase from the hyperthermophile Sulfolobus solfataricus: possible determinants of protein stability. Structure. vol 3, pp. 1295–1306.
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