Dynamic Nature of Proteins is Critically Important for Their Function: GPCRs and Signal Transducers

Proteins and their complexes in structures solved by X-ray crystallography or cryo-EM look rigid. While these structures yield very detailed information, they do not capture critically important property of proteins, their dynamic nature. The very fact that proteins function indicates that they must have moving parts. Structural studies have additional caveats: to obtain structures, proteins are often drastically engineered and placed into highly non-physiological conditions. In contrast to structural studies, biophysical methods, such as EPR and NMR spectroscopy, reveal protein and complex dynamics. Importantly, minimally mutated, virtually wild-type proteins can be used. Here, this issue is discussed using GPCRs and their signal transducers, G proteins and arrestins, as examples. To understand how proteins actually work in living cells, we must keep in mind the limitations of different methods and synthesize the information obtained by all of them.