Probing Conformational Exchange Dynamics in a Short-Lived Protein Folding Intermediate by Real-Time Relaxation-Dispersion NMR

摘要

NMR spectroscopy is a powerful tool for studying molecular dynamics at atomic resolution simultaneously for a large number of nuclear sites. In this communication, we combine two powerful NMR techniques, relaxation--dispersion NMR and real-time NMR, in order to obtain unprecedented information on the conformational exchange dynamics present in shortlived excited protein states, such as those transiently accumulated during protein folding. We demonstrate the feasibility of the approach for the amyloidogenic protein β2-microglobulin that folds via an intermediate state which is believed to be responsible for the onset of the aggregation process leading to amyloid formation.