title: 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.
authors.affiliation: University of Grenoble Alpes , IBS, 38044 Grenoble, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Schneider
authors.forename: Damien
authors.initials: D
authors.lastname: Maurin
authors.forename: Guillaume
authors.initials: G
authors.lastname: Communie
authors.forename: Jaka
authors.initials: J
authors.lastname: Kragelj
authors.forename: D Flemming
authors.initials: DF
authors.lastname: Hansen
authors.forename: Rob W H
authors.initials: RW
authors.lastname: Ruigrok
authors.forename: Malene Ringkjøbing
authors.initials: MR
authors.lastname: Jensen
authors.forename: Martin
authors.initials: M
authors.lastname: Blackledge
mesh_terms: D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009698:Nucleoproteins / Q000737:chemistry*; D010750:Phosphoproteins / Q000737:chemistry*; D029082:Sendai virus / Q000737:chemistry*
chemical_list: D009698:Nucleoproteins; D010750:Phosphoproteins