Visualizing the molecular recognition trajectory of an intrinsically disordered protein using multinuclear relaxation dispersion NMR.

Abstract : Despite playing important roles throughout biology, molecular recognition mechanisms in intrinsically disordered proteins remain poorly understood. We present a combination of (1)H(N), (13)C', and (15)N relaxation dispersion NMR, measured at multiple titration points, to map the interaction between the disordered domain of Sendai virus nucleoprotein (NT) and the C-terminal domain of the phosphoprotein (PX). Interaction with PX funnels the free-state equilibrium of NT by stabilizing one of the previously identified helical substates present in the prerecognition ensemble in a nonspecific and dynamic encounter complex on the surface of PX. This helix then locates into the binding site at a rate coincident with intrinsic breathing motions of the helical groove on the surface of PX. The binding kinetics of complex formation are thus regulated by the intrinsic free-state conformational dynamics of both proteins. This approach, providing high-resolution structural and kinetic information about a complex folding and binding interaction trajectory, can be applied to a number of experimental systems to provide a general framework for understanding conformational disorder in biomolecular function.
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Article dans une revue
Journal of the American Chemical Society, American Chemical Society, 2015, 137 (3), pp.1220-9
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http://hal.univ-grenoble-alpes.fr/hal-01132326
Contributeur : Frank Thomas <>
Soumis le : mardi 17 mars 2015 - 08:55:14
Dernière modification le : lundi 19 février 2018 - 14:34:03

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  • HAL Id : hal-01132326, version 1
  • PUBMED : 25551399

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Robert Schneider, Damien Maurin, Guillaume Communie, Jaka Kragelj, D Flemming Hansen, et al.. Visualizing the molecular recognition trajectory of an intrinsically disordered protein using multinuclear relaxation dispersion NMR.. Journal of the American Chemical Society, American Chemical Society, 2015, 137 (3), pp.1220-9. 〈hal-01132326〉

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