Probing Na(+)-induced changes in the HIV-1 TAR conformational dynamics using NMR residual dipolar couplings: new insights into the role of counterions and electrostatic interactions in adaptive recognition.

Probing Na(+)-induced changes in the HIV-1 TAR conformational dynamics using NMR residual dipolar couplings: new insights into the role of counterions and electrostatic interactions in adaptive recognition. Research Abstract Details 

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Probing Na(+)-induced changes in the HIV-1 TAR conformational dynamics using NMR residual dipolar couplings: new insights into the role of counterions and electrostatic interactions in adaptive recognition. Abstract Text:

Anette Casiano-Negroni,Xiaoyan Sun,Hashim M Al-Hashimi,

Many regulatory RNAs undergo large changes in structure upon recognition of proteins and ligands, but the mechanism by which this occurs remains poorly understood. Using NMR residual dipolar coupling (RDCs), we characterized Na+-induced changes in the structure and dynamics of the bulge-containing HIV-1 transactivation response element (TAR) RNA that mirrors changes induced by small molecules bearing a different number of cationic groups. Increasing the Na+ concentration from 25 to 320 mM led to a continuous reduction in the average inter-helical bend angle (from 46 degrees to 22 degrees ), inter-helical twist angle (from 66 degrees to -18 degrees ), and inter-helix flexibility (as measured by an increase in the internal generalized degree of order from 0.56 to 0.74). Similar conformational changes were observed with Mg2+, indicating that nonspecific electrostatic interactions drive the conformational transition, although results also suggest that Na+ and Mg2+ may associate with TAR in distinct modes. The transition can be rationalized on the basis of a population-weighted average of two ensembles comprising an electrostatically relaxed bent and flexible TAR conformation that is weakly associated with counterions and a globally rigid coaxial conformation that has stronger electrostatic potential and association with counterions. The TAR inter-helical orientations that are stabilized by small molecules fall around the metal-induced conformational pathway, indicating that counterions may help predispose the TAR conformation for target recognition. Our results underscore the intricate sensitivity of RNA conformational dynamics to environmental conditions and demonstrate the ability to detect subtle conformational changes using NMR RDCs.

Probing Na(+)-induced changes in the HIV-1 TAR conformational dynamics using NMR residual dipolar couplings: new insights into the role of counterions and electrostatic interactions in adaptive recognition. Publishing Authors By Initials

A Casiano-Negroni,X Sun,HM Al-Hashimi,

For similar genetic processes: gene expression regulation: trans-activation (genetics) research abstracts see: genetic processes: gene expression regulation: trans-activation (genetics) research

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Probing Na(+)-induced changes in the HIV-1 TAR conformational dynamics using NMR residual dipolar couplings: new insights into the role of counterions and electrostatic interactions in adaptive recognition. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Biochemistry

VOLUME: 46

Page Numbers: 6525-35

Journal Abbreviation: Biochemistry

ISSN: 0006-2960

DAY: 9

MONTH: 05

YEAR: 2007

Probing Na(+)-induced changes in the HIV-1 TAR conformational dynamics using NMR residual dipolar couplings: new insights into the role of counterions and electrostatic interactions in adaptive recognition. Information

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LANGUAGE: eng

NlmUniqueID: 370623

Probing Na(+)-induced changes in the HIV-1 TAR conformational dynamics using NMR residual dipolar couplings: new insights into the role of counterions and electrostatic interactions in adaptive recognition. Keywords Mesh Terms:

KEYWORDS: Trans-Activation (Genetics)

MESH TERMS: genetics

Chemical & Substance for Abstract: Probing Na(+)-induced changes in the HIV-1 TAR conformational dynamics using NMR residual dipolar couplings: new insights into the role of counterions and electrostatic interactions in adaptive recognition. Information

Substance Name: Sodium

Registry Number: 7440-23-5

Grant and Affiliation Information for Probing Na(+)-induced changes in the HIV-1 TAR conformational dynamics using NMR residual dipolar couplings: new insights into the role of counterions and electrostatic interactions in adaptive recognition.

AFFILIATION: Department of Chemistry, Biophysics Research Division, and Program in Bioinformatics, The University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109-1055, USA.

Country: United States

AGENCY: United States NIAID

GRANT: R01 AI066975-01

ACRONYM: AI

MEDLINETA: Biochemistry

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