Proteins move! Protein dynamics and long-range allostery in cell signaling

An emerging point of view in protein chemistry is that proteins are not the static objects that are displayed in textbooks but are instead dynamic actors. Protein dynamics plays a fundamental role in many diseases, and spans a large hierarchy of timescales, from picoseconds to milliseconds or even longer. Nanoscale protein domain motion on length scales comparable to protein dimensions is key to understanding how signals are relayed through multiple protein-protein interactions. A canonical example is how the scaffolding proteins NHERF1 and ezrin work in coordination to assemble crucial membrane complexes. As membrane-cytoskeleton scaffolding proteins, these provide excellent prototypes for understanding how regulatory signals are relayed through protein-protein interactions between the membrane and the cytoskeleton. Here, we review recent progress in understanding the structure and dynamics of the interaction. We describe recent novel applications of neutron spin echo spectroscopy to reveal the dynamic propagation of allosteric signals by nanoscale protein motion, and present a guide to the future study of dynamics and its application to the cure of disease.