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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
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
Abstract:   (4046 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.
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Article Type: Original Research | Subject: Pharmaceutical Biotechnology
Received: 2018/09/16 | Accepted: 2019/09/7 | Published: 2020/03/18

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