Probing Transient Conformational States of Proteins by Solid-State R1ρ Relaxation-Dispersion NMR Spectroscopy

• Published in: Angewandte Chemie International Edition 2014-04, Vol.53 (17), p.4312-4317
• Main Authors: Ma, Peixiang, Haller, Jens D., Zajakala, Jérémy, Macek, Pavel, Sivertsen, Astrid C., Willbold, Dieter, Boisbouvier, Jérôme, Schanda, Paul
• Format: Article
• Language: English
• Subjects: Communications; protein dynamics; relaxation dispersion; solid-state NMR spectroscopy; transient conformations; ubiquitin
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201311275

The function of proteins depends on their ability to sample a variety of states differing in structure and free energy. Deciphering how the various thermally accessible conformations are connected, and understanding their structures and relative energies is crucial in rationalizing protein function. Many biomolecular reactions take place within microseconds to milliseconds, and this timescale is therefore of central functional importance. Here we show that R1ρ relaxation dispersion experiments in magic‐angle‐spinning solid‐state NMR spectroscopy make it possible to investigate the thermodynamics and kinetics of such exchange process, and gain insight into structural features of short‐lived states. Functionally relevant states of proteins are often only short‐lived, and thus difficult to detect. Relaxation‐dispersion experiments in magic‐angle‐spinning solid‐state NMR spectroscopy provide access to such transient states. Information about the exchange kinetics, relative populations, and structures of the short‐lived state can be obtained.