Transmembrane Domains of Bitopic Proteins as a Key to Understand the Cellular Signaling (A Review)

Russian Journal of Bioorganic Chemistry. 2024. Vol. 50. No. 4. P. 1202–1214.

Polyansky A. A., R. G. Efremov

This study presents in a systematic manner the key modeling results corroborated by experimental
biophysical data and obtained by the authors during long-term research on bitopic (single-pass) membrane proteins
(BMPs), which are the crucial elements of cell signaling. The manuscript does not claim to be a comprehensive
review of the subject of interest, whereby the authors did not aim to describe accurately the current state of the
art, given the numerous reliable publications. Rather, this is an essay illustrating the authors’ understanding of the
basic principles of organization of protein transmembrane domains (TMDs) and of their contribution to the cell
functioning. Among the key topics highlighted in the present study are the fine-tuned processes of TMD
oligomerization and the direct contribution from the dynamic membrane environment to this process, as well as the
key role of TMD in the functioning of cell receptors and mutual relations between all the components of proteinmembrane
complexes during the signal transduction in normal and pathological conditions.

Keywords: молекулярная динамика, membrane proteins, мембранные белки, protein-lipid interactions, белок-липидные взаимодействия, molecular dynamics, Oligomerization, олигомеризация, molecular-biophysical platform, “membrane response”, allosteric communication in proteins, Молекулярно-биофизическая платформа, “мембранный ответ”, аллостерическая коммуникация в белках