Time-Resolved Protein Side-Chain Motions Unraveled by High- Resolution Relaxometry and Molecular Dynamics Simulations

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Time-Resolved Protein Side-Chain Motions Unraveled by High-Resolution Relaxometry and Molecular Dynamics Simulations, Journal of the American Chemical Society, Volume 140, p. 13456 - 13465, 2018



Well-folded proteins are described by structural models of high precision obtained by X-ray crystallography, NMR, and cryoelectron microscopy. Yet, at ambient conditions extensive internal motions occur throughout all proteins, on time scales ranging from the picosecond to seconds and beyond. Such motions include local librations in the picosecond range, slower rotameric jumps of protein side chains, diffusive motions of loops or entire domains, as well as conformational transitions that involve signifi cant energy barriers and take place on slower time scales of microseconds to seconds. The motions of protein side chains are essential to protein function. For example, the malleability of side chains at the surface of proteins enables them to engage in specific interactions with multiple targets, while the hydrophobic side chains in the core of a protein constitute a fluid-like entropy reservoir, which decisively contributes to its thermodynamic properties.



We have introduced a novel method, based on the combination of high-resolution relaxometry with high-field relaxation measurements, to obtain an unprecedented detailed view of protein side-chain motions on picosecond-to-nanosecond time scales. We have quantitatively characterized motions of the isoleucine side chains of the protein ubiquitin with correlation times covering 3 orders of magnitude. Importantly, we have identified motions in the low-nanosecond range for three out of seven isoleucine side chains. The nature of these motions was investigated with molecular dynamics simulations.


N'hésitez pas à consulter le communiqué de presse associé à cet article : Mouvements des protéines : la valse des chaînes latérales



Journal of the American Chemical SocietyVolume 140, p. 13456 - 13465, 2018


Motions of proteins are essential for the performance of their functions. Aliphatic protein side chains and their motions play critical roles in protein interactions: for recognition and binding of partner molecules at the surface or serving as an entropy reservoir within the hydrophobic core. Here, we present a new NMR method based on highresolution relaxometry and high-fi eld relaxation to determine quantitatively both motional amplitudes and time scales of methyl-bearing side chains in the picosecond-to-nanosecond range. We detect a wide variety of motions in isoleucine side chains in the protein ubiquitin. We unambiguously identify slow motions in the low nanosecond range, which, in conjunction with molecular dynamics computer simulations, could be assigned to transitions between rotamers. Our approach provides unmatched detailed insight into the motions of aliphatic side chains in proteins and provides a better understanding of the nature and functional role of protein side-chain motions.


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Time-Resolved Protein Side-Chain Motions Unraveled by High-Resolution Relaxometry and Molecular Dynamics Simulations


Samuel F. Cousin, Pavel Kadeřávek, Nicolas Bolik-Coulon, Yina Gu, Cyril Charlier, Ludovic Carlier, Lei Bruschweiler-Li, Thorsten Marquardsen, Jean-Max Tyburn, Rafael Brüschweiler and Fabien Ferrage


Journal of the American Chemical Society, Volume 140, p. 13456 - 13465, 2018


DOI :10.1021/jacs.8b09107