Equilibrium dynamics of a biomolecular complex analyzed at single-amino acid resolution by cryo-electron microscopy
The biological function of macromolecular complexes depends not only on large-scale transitions between conformations, but also on small-scale conformational fluctuations at equilibrium. This study shows that detailed information on the equilibrium dynamics of a biocomplex obtained from local resolution (LR) data in cryo-electron microscopy (cryo-EM) density maps matches the information obtained in solution by hydrogen-deuterium exchange mass-spectrometry. The structure of the minute virus of mice (MVM) capsid as a model system was determined by cryo-EM, and LR values were found to correlate with both crystallographic B-factors and hydrogen-deuterium exchange values. Once validated, the cryo-EM LR-based approach was used to compare the equilibrium dynamics of wild-type and two mutant MVM capsids. The results revealed a linkage between mechanical stiffening and impaired equilibrium dynamics in a biocomplex. Cryo-EM is emerging as a powerful approach for simultaneously acquiring information on the atomic structure and local equilibrium dynamics of biomolecular complexes.