NMR and smFRET insights into fast protein motions and their relation to function

Proteins often undergo large-scale conformational transitions, in which secondary and tertiary structure elements (loops, helices and domains) change their structures or their positions with respect to each other. Simple considerations suggest that such dynamics should be relatively fast, while the functional cycles of many proteins are often relatively slow. Sophisticated experimental methods are starting to tackle this dichotomy and shed light on the contribution of large-scale conformational dynamics to protein function. In this review we focus on the contribution of single-molecule FRET and NMR spectroscopies to the study of conformational dynamics. We describe briefly the state-of-the- art in each of each of these techniques and then point to their similarities and differences, as well as to the relative strengths and weaknesses of each. Several case studies in which the connection between fast conformational dynamics and slower function has been demonstrated are then introduced and discussed. These examples include both enzymes and large protein machines, some of which have been studied by both NMR and fluorescence spectroscopies.