Abstract
Despite playing important roles throughout biology, molecular recognition mechanisms in intrinsically disordered proteins remain poorly understood. We present a combination of 1HN, 13C' and 15N relaxation dispersion (RD) 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 sub-states present in the pre-recognition ensemble, in a non-specific 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 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.
PMID: 25551399 [PubMed - as supplied by publisher]
[NMR paper] Solid-State (13)C NMR Reveals Annealing of Raft-Like Membranes Containing Cholesterol by the Intrinsically Disordered Protein ?-Synuclein.
Solid-State (13)C NMR Reveals Annealing of Raft-Like Membranes Containing Cholesterol by the Intrinsically Disordered Protein ?-Synuclein.
Related Articles Solid-State (13)C NMR Reveals Annealing of Raft-Like Membranes Containing Cholesterol by the Intrinsically Disordered Protein ?-Synuclein.
J Mol Biol. 2013 Apr 11;
Authors: Leftin A, Job C, Beyer K, Brown MF
Abstract
Misfolding and aggregation of the intrinsically disordered protein ?-Synuclein (?S) in Lewy body plaques is a characteristic marker of late-stage Parkinson's disease. It is...
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Solid-State 13C NMR Reveals Annealing of Raft-Like Membranes Containing Cholesterol by the Intrinsically Disordered Protein ?-Synuclein
Solid-State 13C NMR Reveals Annealing of Raft-Like Membranes Containing Cholesterol by the Intrinsically Disordered Protein ?-Synuclein
Publication date: Available online 11 April 2013
Source:Journal of Molecular Biology</br>
Author(s): Avigdor Leftin , Constantin Job , Klaus Beyer , Michael F. Brown</br>
Misfolding and aggregation of the intrinsically disordered protein ?-Synuclein (?S) in Lewy body plaques is a characteristic marker of late-stage Parkinson’s disease. It is well established that membrane binding is initiated at the N-terminus of the protein and...
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04-11-2013 09:27 PM
[NMR paper] Probing Local Backbone Geometries in Intrinsically Disordered Proteins by Cross-Correlated NMR Relaxation.
Probing Local Backbone Geometries in Intrinsically Disordered Proteins by Cross-Correlated NMR Relaxation.
Probing Local Backbone Geometries in Intrinsically Disordered Proteins by Cross-Correlated NMR Relaxation.
Angew Chem Int Ed Engl. 2013 Mar 20;
Authors: Stanek J, Saxena S, Geist L, Konrat R, Ko?mi?ski W
Abstract
Ab ultra-high-resolution NMR experiment for the measurement of intraresidue (1) H(i)-(15) N(i)-(13) C'(i) dipolar-chemical shift anisotropy relaxation interference is employed to extract information about local backbone...
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03-23-2013 06:36 PM
[NMR paper] Fast hydrogen exchange affects (15)N relaxation measurements in intrinsically disordered proteins.
Fast hydrogen exchange affects (15)N relaxation measurements in intrinsically disordered proteins.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--production.springer.de-OnlineResources-Logos-springerlink.gif Related Articles Fast hydrogen exchange affects (15)N relaxation measurements in intrinsically disordered proteins.
J Biomol NMR. 2013 Jan 12;
Authors: Kim S, Wu KP, Baum J
Abstract
Unprotected amide protons can undergo fast hydrogen exchange (HX) with protons from the solvent. Generally, NMR experiments using the out-and-back...
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02-03-2013 10:22 AM
Deuterium isotope shifts for backbone 1H, 15N and 13C nuclei in intrinsically disordered protein α-synuclein
Deuterium isotope shifts for backbone 1H, 15N and 13C nuclei in intrinsically disordered protein α-synuclein
Abstract Intrinsically disordered proteins (IDPs) are abundant in nature and characterization of their potential structural propensities remains a widely pursued but challenging task. Analysis of NMR secondary chemical shifts plays an important role in such studies, but the output of such analyses depends on the accuracy of reference random coil chemical shifts. Although uniform perdeuteration of IDPs can dramatically increase spectral resolution, a feature particularly...
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09-10-2012 01:48 AM
Microsecond Time-Scale Conformational Exchange in Proteins: Using Long Molecular Dynamics Trajectory To Simulate NMR Relaxation Dispersion Data
Microsecond Time-Scale Conformational Exchange in Proteins: Using Long Molecular Dynamics Trajectory To Simulate NMR Relaxation Dispersion Data
Yi Xue, Joshua M. Ward, Tairan Yuwen, Ivan S. Podkorytov and Nikolai R. Skrynnikov
http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/0/jacsat.ahead-of-print/ja206442c/aop/images/medium/ja-2011-06442c_0001.gif
Journal of the American Chemical Society
DOI: 10.1021/ja206442c
http://feeds.feedburner.com/~ff/acs/jacsat?d=yIl2AUoC8zA
http://feeds.feedburner.com/~r/acs/jacsat/~4/NvRRKHU2H3k
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01-28-2012 05:27 AM
Paramagnetic relaxation enhancement to improve sensitivity of fast NMR methods: application to intrinsically disordered proteins
Paramagnetic relaxation enhancement to improve sensitivity of fast NMR methods: application to intrinsically disordered proteins
Abstract We report enhanced sensitivity NMR measurements of intrinsically disordered proteins in the presence of paramagnetic relaxation enhancement (PRE) agents such as Ni2+-chelated DO2A. In proton-detected 1H-15N SOFAST-HMQC and carbon-detected (H-flip)13CO-15N experiments, faster longitudinal relaxation enables the usage of even shorter interscan delays. This results in higher NMR signal intensities per units of experimental time, without adverse line...