Biochemistry has a strong interest in ion channels, a diverse group of membrane proteins. This group has long remained difficult to study at the structural level, but much progress has been made in recent decades with improvements in biochemical methods and computational procedures. Voltage-gated ion channels undergo conformational changes upon functioning, and multiple models of activation mechanisms were proposed based on experimental data. This review focuses on the structural studies of the functioning of voltage-gated ion channels, which are accompanied by conformational changes in proteins, and the methodological advances that allow their observation. Particular attention is paid to the lipid modulation of ion channels, as well as to the use of various lipids and membrane mimetics to stabilize specific conformations of ion channels. Modern experimental methods that allow obtaining ion channel proteins in specific functional states are discussed, including cryoelectron microscopy and cryoelectron tomography. NMR (Nuclear Magnetic Resonance) spectroscopy approaches and molecular modeling studies of conformational dynamics of ion channels and their isolated domains are also discussed. Finally, new algorithms for studying the conformational mobility of proteins have been recently developed, which help to better understand the mechanisms of ion channel domain movements.
Sokolova et al. (Wed,) studied this question.