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Iranian Biomedical Journal، جلد ۲۷، شماره ۴، صفحات ۱۹۱-۱۹۸
عنوان فارسی
چکیده فارسی مقاله
کلیدواژه‌های فارسی مقاله
عنوان انگلیسی Engineering a CEACAM1 Variant with the Increased Binding Affinity to TIM-3 Receptor
چکیده انگلیسی مقاله
Background: T-cell immunoglobulin domain and mucin domain-3 (TIM-3) is an inhibitory receptor expressed in a variety of cells, including dendritic cells, T-helper 1 lymphocytes, and natural killer cells. Binding of this protein to its ligand, carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), causes T-cell exhaustion, a specific condition in which effector T cells lose their ability to proliferate and produce cytokines. Blocking this inhibitory receptor is known to be an effective strategy for treating cancer and other related diseases. Therefore, in this study, in order to block the inhibitory receptor of TIM-3, we designed and produced recombinantly a protein with a high binding affinity to this receptor.
Methods: The extracellular domain of CEACAM1 involved in binding to TIM-3 was mutated using R script to obtain a variant with the increased binding affinity to TIM-3. The binding energy of the mutant protein was calculated using the FoldX module. Finally, after recombinant production of the most appropriate CEACAM1 variant (variant 39) in E. coli, its secondary structure was determined by CD spectroscopy.
Results: The binding free energy between variant 39 and TIM-3 decreased from -5.63 to -14.49 kcal/mol, indicating an increased binding affinity to the receptor. Analysis of the secondary structure of this variant also showed that the mutation did not significantly alter the structure of the protein.
Conclusion: Our findings suggest that variant 39 could bind to TIM-3 with a higher binding affinity than the wild-type, making it a proper therapeutic candidate for blocking TIM-3.
کلیدواژه‌های انگلیسی مقاله Binding affinity, Mutagenesis, TIM-3 protein
نویسندگان مقاله | Zahra Hajihassan
Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran


| Mehran Mohammadpour saray
Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran


| Aysan Yaseri
Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran
نشانی اینترنتی http://ibj.pasteur.ac.ir/browse.php?a_code=A-10-1667-2&slc_lang=en&sid=1
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کد مقاله (doi)
زبان مقاله منتشر شده en
موضوعات مقاله منتشر شده Pharmaceutical Biotechnology
نوع مقاله منتشر شده مقاله کامل
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