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

J Am Chem Soc. 2015 Jan 28;137(3):1220-9. doi: 10.1021/ja511066q. Epub 2015 Jan 16.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular*
  • Nucleoproteins / chemistry*
  • Phosphoproteins / chemistry*
  • Sendai virus / chemistry*


  • Nucleoproteins
  • Phosphoproteins