Conformational features of HVEM protein upon its cis and trans binding to BTLA protein
https://doi.org/10.29235/1561-8323-2024-68-6-460-464
Abstract
T-cell activation begins upon antigenic recognition by T-cell receptor and is regulated by signals generated by co-stimulating and co-inhibiting molecules. These molecules, known as immune checkpoints, are attractive therapeutic targets for the therapy of cancer and autoimmune diseases. Co-inhibiting signal pathway formed between TNF-receptor HVEM (Herpes- Virus Entry Mediator, TNFRSF14) and BTLA (B and T Lymphocyte Attenuator) limits T-cell activation. However, BTLA can serve also as activating ligand when interacts with HVEM on adjacent cell. Mutagenesis experiments have shown that the same interface is formed between HVEM and BTLA both upon cis and trans interactions thus suggesting significant conformational rearrangement in the HVEM stalk region between ectodomain and transmembrane domains upon transfer from cis to trans binding to BTLA. However, because of technical problems of the crystallization of surface receptor with long stalks, HVEM atomistic 3D-structures including stalk region are absent up to now. In this study, the approaches of structural bioinformatics were used to determine the structures of full-length proteins HVEM and BTLA and their complexes upon cis- and trans-interactions. The results obtained can be used upon developing immunoregulators for the immunotherapy of cancer and autoimmune diseases.
Supporting agencies: The work has been sponsored by the Belarusian Republican Foundation for Fundamental Research (Grant Б22-016).
About the Authors
V. A. Urban
Institute of Biophysics and Cell Engineering of the National Academy of Sciences of Belarus
Belarus
Belarus
Urban Viktar A. – Ph. D. (Biology), Senior Researcher
27, Akademicheskaya Str., 220072, Minsk
F. O. Kanstantinau
Institute of Biophysics and Cell Engineering of the National Academy of Sciences of Belarus
Belarus
Belarus
Kanstantinau Frants O. – Postgraduate Student
27, Akademicheskaya Str., 220072, Minsk
V. G. Veresov
Institute of Biophysics and Cell Engineering of the National Academy of Sciences of Belarus
Belarus
Belarus
Veresov Valery G. – D. Sc. (Biology), Chief Researcher
27, Akademicheskaya Str., 220072, Minsk
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