[NMR paper] A General Method for Constructing Atomic-Resolution RNA Ensembles using NMR Residual Dipolar Couplings: The Basis for Inter-helical Motions Revealed.

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A General Method for Constructing Atomic-Resolution RNA Ensembles using NMR Residual Dipolar Couplings: The Basis for Inter-helical Motions Revealed.

Related Articles A General Method for Constructing Atomic-Resolution RNA Ensembles using NMR Residual Dipolar Couplings: The Basis for Inter-helical Motions Revealed.

J Am Chem Soc. 2013 Mar 8;

Authors: Salmon L, Bascom GD, Andricioaei I, Al-Hashimi HM

Abstract
The ability to modulate alignment and measure multiple independent sets of NMR residual dipolar couplings (RDCs) has made it possible to characterize internal motions in proteins at atomic resolution and with timescale sensitivity ranging from picoseconds up to milliseconds. The application of such methods to the study of RNA dynamics, however, remains fundamentally limited by the inability to modulate alignment and by strong couplings between internal and overall motions that complicate the quantitative interpretation of RDCs. Here, we address this problem by showing that RNA alignment can be generally modulated, in a controlled manner, by variable elongation of A-form helices, and that the information contained within the measured RDCs can be extracted even in the presence of strong couplings between motions and overall alignment via structure-based prediction of alignment. Using this approach, four RDC data sets, and a broad conformational pool obtained from a 8.2?s molecular dynamics simulation, we successfully construct and validate an atomic resolution ensemble of HIV-1 TAR RNA. This ensemble reveals local motions in and around the bulge involving changes in stacking and hydrogen bonding interactions, which are undetectable by traditional spin relaxation and that drive global changes in inter-helical orientation. This new approach broadens the scope of using RDCs in characterizing the dynamics of nucleic acids.


PMID: 23473378 [PubMed - as supplied by publisher]



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