Menu
Institut de Biologie StructuraleGrenoble / France

A Unified Description of Intrinsically Disordered Protein Dynamics under Physiological Conditions using NMR Spectroscopy

Scientists estimate that one third of human proteins are intrinsically disordered proteins (IDPs), i.e. proteins without a stable three-dimensional structure. Very flexible, these biomolcules can adapt to several physiological partners and adopt a multitude of conformations. Their functioning remains poorly understood even though they play essential roles in all living organisms. Nuclear magnetic resonance (NMR) spectroscopy is ideally suited to the investigation of this behavior at atomic resolution.
In this study, measuring an extensive set of relaxation rates sampling multiple-time-scale dynamics over a broad range of crowding conditions, the researchers of the FDP group of the IBS develop and test an integrated analytical description that accurately portrays the motion of IDPs as a function of the intrinsic properties of the crowded molecular environment. In particular they observe a strong dependence of both short-range and long-range motional time scales of the protein on the friction of the solvent. This tight coupling between the dynamic behavior of the IDP and its environment allows them to develop analytical expressions for protein motions and NMR relaxation properties that can be accurately applied over a vast range of experimental conditions. This unified dynamic description provides new insight into the physical behavior of IDPs, extending their ability to quantitatively investigate their conformational dynamics under complex environmental conditions, and accurately predicting relaxation rates reporting on motions on time scales up to tens of nanoseconds, both in vitro and in cellulo.

A Unified Description of Intrinsically Disordered Protein Dynamics under Physiological Conditions using NMR Spectroscopy. Wiktor Adamski, Nicola Salvi, Damien Maurin, Justine Magnat, Sigrid Milles, Malene Ringkjøbing Jensen, Anton Abyzov, Christophe Moreau, Martin Blackledge. Journal of the American Chemical Society ; 141(44):17817-17829