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Pesaran Afsharian N, Hajihassan Z, Ansari-Pour N. Target Mutation of CD80 Protein to Enhance Its Binding to CD28 Receptor. JMBS 2020; 11 (1) :1-11
URL: http://biot.modares.ac.ir/article-22-24342-en.html
URL: http://biot.modares.ac.ir/article-22-24342-en.html
1- Department of life science engineering, Faculty of new sciences and technologies, University of Tehran, Tehran, Iran
2- Life Science Engineering Department, New Sciences & Technologies Faculty, University of Tehran, Tehran, Iran, New Sciences & Technologies Faculty, North Kargar Street, Next to the Jalale Ale Ahmad Crossroads, Tehran, Iran. Postal Code: 1439957131 ,hajihasan@ut.ac.ir
3- Life Science Engineering Department, New Sciences & Technologies Faculty, University of Tehran, Tehran, Iran
2- Life Science Engineering Department, New Sciences & Technologies Faculty, University of Tehran, Tehran, Iran, New Sciences & Technologies Faculty, North Kargar Street, Next to the Jalale Ale Ahmad Crossroads, Tehran, Iran. Postal Code: 1439957131 ,
3- Life Science Engineering Department, New Sciences & Technologies Faculty, University of Tehran, Tehran, Iran
Abstract: (7250 Views)
The CD80 protein, a member of the super-family of immunoglobulin, is a transmembrane protein expressed on the surface of the antigen-presenting cells (APC). This protein has two receptors on the surface of T cells (CTLA-4 and CD28), due to the binding of this protein to these receptors, the inhibitory and stimulatory pathway in the T cells begin, respectively. Naturally, CD80 proteins tend to have more binding affinity to CTLA-4 than CD28, and this is a factor in the extinction of T cells in the immune system in order to prevent autoimmunity. The aim of the present study is to create a variant of the CD80 protein that has an increased binding affinity to CD28 to bind to this receptor more strongly and induce more simulate pathways than the wild type of this protein (primary CD80 protein) in T cells. To identify this variant, first, the ancestral sequence was mutated by R software at positions 31 and 92 with amino acids that play an important role in the formation of hydrogen bonds. The R software output sequences were modeled with the SWISS-MODEL server. Then, each output model was docked with the HADDOCK server, and finally, the electrostatic and van der Waals energies between the receptors and the ligands were calculated. Among all the built-in models, the mutated K31Y, R92F has the best electrostatic and van der Waals energies and has the ability to have a much better connection to its CD28 receptor compared to the ancestral type of CD80.
Article Type: Original Research |
Subject:
Pharmaceutical Biotechnology
Received: 2018/09/16 | Accepted: 2019/09/7 | Published: 2020/03/18
Received: 2018/09/16 | Accepted: 2019/09/7 | Published: 2020/03/18
References
1. Van Der Merwe PA, Dushek O. Mechanisms for T cell receptor triggering. Nat Rev Immunol. 2011;11(1):47-55. [Link] [DOI:10.1038/nri2887]
2. Gardner D, Jeffery LE, Sansom DM. Understanding the CD28/CTLA‐4 (CD152) pathway and its implications for costimulatory blockade. Am J Transplant. 2014;14(9):1985-91. [Link] [DOI:10.1111/ajt.12834]
3. Bajorath J, Peach RJ, Linsley PS. Immunoglobulin fold characteristics of B7-1 (CD80) and B7-2 (CD86). Protein Sci. 1994;3(11):2148-50. [Link] [DOI:10.1002/pro.5560031128]
4. Callahan MK, Wolchok JD, Allison JP. Anti-CTLA-4 antibody therapy: Immune monitoring during clinical development of a novel immunotherapy. Semin Oncol. 37(5):473-84. [Link] [DOI:10.1053/j.seminoncol.2010.09.001]
5. Lipson EJ, Drake CG. Ipilimumab: An anti-CTLA-4 antibody for metastatic melanoma. Clin Cancer Res. 2011;17(22):6958-62. [Link] [DOI:10.1158/1078-0432.CCR-11-1595]
6. Bertrand A, Kostine M, Barnetche T, Truchetet ME, Schaeverbeke T. Immune related adverse events associated with anti-CTLA-4 antibodies: Systematic review and meta-analysis. BMC Med. 2015;13(1):211. [Link] [DOI:10.1186/s12916-015-0455-8]
7. Quirk SK, Shure AK, Agrawal DK. Immune-mediated adverse events of anticytotoxic T lymphocyte-associated antigen 4 antibody therapy in metastatic melanoma. Transl Res. 2015;166(5):412-24. [Link] [DOI:10.1016/j.trsl.2015.06.005]
8. Kähler KC, Hassel JC, Heinzerling L, Loquai C, Mössner R, Ugurel S, et al. Management of side effects of immune checkpoint blockade by anti‐CTLA‐4 and anti‐PD‐1 antibodies in metastatic melanoma. JDDG: Journal der Deutschen Dermatologischen Gesellschaft. 2016;14(7):662-81. [Link] [DOI:10.1111/ddg.13047]
9. Schwede T, Kopp J, Guex N, Peitsch MC. SWISS-MODEL: An automated protein homology-modeling server. Nucleic Acids Res. 2003;31(13):3381-5. [Link] [DOI:10.1093/nar/gkg520]
10. UniProt Consortium. UniProt: A hub for protein information. Nucleic Acids Res. 2015;43:D204-12. [Link] [DOI:10.1093/nar/gku989]
11. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, et al. UCSF Chimera-a visualization system for exploratory research and analysis. J Comput Chem. 2004;25(13):1605-12. [Link] [DOI:10.1002/jcc.20084]
12. Dominguez C, Boelens R, Bonvin AM. HADDOCK: A protein-protein docking approach based on biochemical or biophysical information. J Am Chem Soc. 2003;125(7):1731-7. [Link] [DOI:10.1021/ja026939x]
13. Sørensen P, Kussmann M, Rosén A, Bennett KL, Da Graça Thrige D, Uvebrant K, et al. Identification of protein-protein interfaces implicated in CD80-CD28 costimulatory signaling. J Immunol. 2004;172(11):6803-9. [Link] [DOI:10.4049/jimmunol.172.11.6803]
14. Kim DE, Chivian D, Baker D. Protein structure prediction and analysis using the Robetta server. Nucleic Acids Res. 2004;32(suppl-2):W526-31. [Link] [DOI:10.1093/nar/gkh468]
15. Ihaka R, Gentleman R. R: A language for data analysis and graphics. J Comput Graph Stat. 1996;5(3):299-314. [Link] [DOI:10.1080/10618600.1996.10474713]
16. Evans EJ, Esnouf RM, Manso-Sancho R, Gilbert RJ, James JR, Yu C, et al. Crystal structure of a soluble CD28-Fab complex. Nat Immunol. 2005;6(3):271-9. [Link] [DOI:10.1038/ni1170]
17. Davis AM, Plowright AT, Valeur E. Directing evolution: The next revolution in drug discovery?. Nat Rev Drug Discov. 2017;16(10):681-98. [Link] [DOI:10.1038/nrd.2017.146]
18. Maute RL, Gordon SR, Mayer AT, McCracken MN, Natarajan A, Ring NG, et al. Engineering high-affinity PD-1 variants for optimized immunotherapy and immuno-PET imaging. Proc Natl Acad Sci. 2015;112(47):E6506-14. [Link] [DOI:10.1073/pnas.1519623112]
19. Pascolutti R, Sun X, Kao J, Maute RL, Ring AM, Bowman GR, et al. Structure and dynamics of PD-L1 and an ultra-high-affinity PD-1 receptor mutant. Structure. 2016;24(10):1719-28. [Link] [DOI:10.1016/j.str.2016.06.026]
20. Ellmark P, Furebring C, Dahlen E, inventors. CD86 variants with improved affinity for CTLA-4. U.S. Patent No. 9834589. 2017. [Link]
21. Swanson R, Kornacker M, Demonte DW, Maurer MF, inventors. CD80 variant immunomodulatory proteins and uses thereof. U.S. Patent Application No. 16320981. 2019. [Link]
22. Khalil DN, Smith EL, Brentjens RJ, Wolchok JD. The future of cancer treatment: Immunomodulation, CARs and combination immunotherapy. Nat Rev Clin Oncol. 2016;13(5):273-90. [Link] [DOI:10.1038/nrclinonc.2016.25]
23. Bornscheuer UT, Hauer B, Jaeger KE, Schwaneberg U. Directed evolution empowered redesign of natural proteins for the sustainable production of chemicals and pharmaceuticals. Angew Chem Int Ed. 2019;58(1):36-40. [Link] [DOI:10.1002/anie.201812717]
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