A Physical Picture of Atomic Motions within the Dickerson DNA Dodecamer in Solution Derived from Joint Ensemble Refinement against NMR and Large-Angle X-ray Scattering Data

Schwieters, Charles D.; Clore, G. Marius

doi:10.1021/bi061943x

Cited by 94 publications

(133 citation statements)

References 62 publications

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“…Recent success with combining NMR and SAXS/WAXS data for refining structural ensembles [32,[45][46][47] has shown that inclusion of global restraints is functionally complementary and successful for NMR structure solution, and our work shows that pump-probe X-ray scattering measurements have decisive value for time-resolved structure determination when used in combination with additional experimental restraints from DEER and NMR. b Ramachandran analysis was conducted on the calculated average structure from the ensemble using Molprobity (http://molprobity.biochem.duke.edu/).…”

Section: Interspin Distance and Distance Distribution Changes In The mentioning

confidence: 77%

The Short-Lived Signaling State of the Photoactive Yellow Protein Photoreceptor Revealed by Combined Structural Probes

Lovett²,

et al. 2011

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J.J.v.T. is a Royal Society University Research Fellow. We thank Gunnar Jeschke for help with initial experiments, for help with DEER data analysis and for valuable discussions. We thank Peter Höfer for access to facilities at Bruker BioSpin, Rheinstetten. We thank Jim McDonnell for help with acquiring NMR data. We acknowledge access to beamline ID09B at the European Synchrotron Radiation Facility under access number SC2438. We thank Michael Wulff for support at beamline ID09B at ESRF. We thank Jungkweon Choi for help with collecting TR-WAXS data. We thank Alexander Grishaev for help with the NIH CNS-SAXS program. J.J.v. Supporting information:Nuclear magnetic resonance, double electron electron resonance, and small angle X-ray scattering tables; figures; and experimental details. This material is available free of charge via the Internet at http://pubs.acs.org reduced folding of the I 2 ′ state (also referred to as the 'pB' state) that is widely reported, but indicates it to be relatively ordered and rearranged. Furthermore, there is direct evidence for the repositioning of the N-terminal region in the I 2 ′ state, which is structurally modeled by dynamical annealing and refinement calculations.

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Section: Interspin Distance and Distance Distribution Changes In The mentioning

confidence: 77%

The Short-Lived Signaling State of the Photoactive Yellow Protein Photoreceptor Revealed by Combined Structural Probes

Lovett²,

et al. 2011

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“…Second, there is a need to develop approaches for modulating alignment of nucleic acids. Only then will it be possible to effectively apply model-free 58,77 and ensemble 81 approaches for the characterization of dynamics with enhanced structural resolution. Finally, the combination of RDCs with other techniques, including spin-relaxation methods and timeresolved NMR discussed in other review articles in this issue promises to lay a basis for unraveling the structural plasticity of RNA over the entire window of biologically relevant timescales.…”

Section: Discussionmentioning

confidence: 99%

Review NMR studies of RNA dynamics and structural plasticity using NMR residual dipolar couplings

et al. 2007

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An increasing number of RNAs are being discovered that perform their functions by undergoing large changes in conformation in response to a variety of cellular signals, including recognition of proteins and small molecular targets, changes in temperature, and RNA synthesis itself. The measurement of NMR residual dipolar couplings (RDCs) in partially aligned systems is providing new insights into the structural plasticity of RNA through combined characterization of large‐amplitude collective helix motions and local flexibility in noncanonical regions over a wide window of biologically relevant timescales (<milliseconds). Here, we review RDC methodology for studying RNA structural dynamics and survey what has been learnt thus far from application of these methods. Future methodological challenges are also identified. © 2007 Wiley Periodicals, Inc. Biopolymers 86: 384–402, 2007.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

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“…Compared with other NMR techniques, RDCs provide long-range angular structure information that helps to generate equilibrium ensemble models (9). In combination with molecular dynamic simulations, RDCs have been used to generate ensemble models for small disordered proteins (7,10), DNA duplexes (11), and a RNA bulge motif (12)(13)(14). In addition to RDCs, relaxation dispersion and paramagnetic relaxation enhancement have been used to detect and characterize conformational states that are in low abundance in an ensemble (5).…”

Section: Helix-junction-helix | Saxsmentioning

confidence: 99%

From a structural average to the conformational ensemble of a DNA bulge

Shi¹,

Beauchamp

Harbury

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Direct experimental measurements of conformational ensembles are critical for understanding macromolecular function, but traditional biophysical methods do not directly report the solution ensemble of a macromolecule. Small-angle X-ray scattering interferometry has the potential to overcome this limitation by providing the instantaneous distance distribution between pairs of gold-nanocrystal probes conjugated to a macromolecule in solution. Our X-ray interferometry experiments reveal an increasing bend angle of DNA duplexes with bulges of one, three, and five adenosine residues, consistent with previous FRET measurements, and further reveal an increasingly broad conformational ensemble with increasing bulge length. The distance distributions for the AAA bulge duplex (3A-DNA) with six different Au-Au pairs provide strong evidence against a simple elastic model in which fluctuations occur about a single conformational state. Instead, the measured distance distributions suggest a 3A-DNA ensemble with multiple conformational states predominantly across a region of conformational space with bend angles between 24 and 85 degrees and characteristic bend directions and helical twists and displacements. Additional X-ray interferometry experiments revealed perturbations to the ensemble from changes in ionic conditions and the bulge sequence, effects that can be understood in terms of electrostatic and stacking contributions to the ensemble and that demonstrate the sensitivity of X-ray interferometry. Combining X-ray interferometry ensemble data with molecular dynamics simulations gave atomic-level models of representative conformational states and of the molecular interactions that may shape the ensemble, and fluorescence measurements with 2-aminopurinesubstituted 3A-DNA provided initial tests of these atomistic models. More generally, X-ray interferometry will provide powerful benchmarks for testing and developing computational methods. helix-junction-helix | SAXSA grand challenge in biology is to understand the complex free-energy landscape of macromolecules and to decipher the resulting conformational ensembles. To perform their biological functions, macromolecules must adopt a multiplicity of conformations. Balancing and controlling different conformational states is central to biological processes including protein folding, allostery and signaling, and the stepwise assembly and function of macromolecular machines. To understand these complex molecules requires characterization of their free-energy landscapes-i.e., their equilibrium conformational ensembles. Precise measurements of conformational ensembles could allow quantitative modeling of the folding and function of biological macromolecules, would provide valuable experimental data to test current computational models and assumptions, and might facilitate the rational design of specifically acting inhibitors (1, 2).Techniques including NMR and EPR relaxation have been developed to incisively probe motions in the ensemble on different time scales, ranging from pic...

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A Physical Picture of Atomic Motions within the Dickerson DNA Dodecamer in Solution Derived from Joint Ensemble Refinement against NMR and Large-Angle X-ray Scattering Data

Cited by 94 publications

References 62 publications

The Short-Lived Signaling State of the Photoactive Yellow Protein Photoreceptor Revealed by Combined Structural Probes

The Short-Lived Signaling State of the Photoactive Yellow Protein Photoreceptor Revealed by Combined Structural Probes

Review NMR studies of RNA dynamics and structural plasticity using NMR residual dipolar couplings

From a structural average to the conformational ensemble of a DNA bulge

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