Transmembrane Domains of Bitopic Proteins As a Key to Understand the Cellular Signaling

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