Characterizing complex dynamics in the transactivation response element apical loop and motional correlations with the bulge by NMR, molecular dynamics, and mutagenesis.

Characterizing complex dynamics in the transactivation response element apical loop and motional correlations with the bulge by NMR, molecular dynamics, and mutagenesis. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Characterizing complex dynamics in the transactivation response element apical loop and motional correlations with the bulge by NMR, molecular dynamics, and mutagenesis. Abstract Text:

The HIV-1 transactivation response element (TAR) RNA binds a variety of proteins and is a target for developing anti-HIV therapies. TAR has two primary binding sites: a UCU bulge and a CUGGGA apical loop. We used NMR residual dipolar couplings, carbon spin relaxation (R(1) and R(2)), and relaxation dispersion (R(1rho)) in conjunction with molecular dynamics and mutagenesis to characterize the dynamics of the TAR apical loop and investigate previously proposed long-range interactions with the distant bulge. Replacement of the wild-type apical loop with a UUCG loop did not significantly affect the structural dynamics at the bulge, indicating that the apical loop and the bulge act largely as independent dynamical recognition centers. The apical loop undergoes complex dynamics at multiple timescales that are likely important for adaptive recognition: U31 and G33 undergo limited motions, G32 is highly flexible at picosecond-nanosecond timescales, and G34 and C30 form a dynamic Watson-Crick basepair in which G34 and A35 undergo a slow (approximately 30 mus) likely concerted looping in and out motion, with A35 also undergoing large amplitude motions at picosecond-nanosecond timescales. Our study highlights the power of combining NMR, molecular dynamics, and mutagenesis in characterizing RNA dynamics.

Characterizing complex dynamics in the transactivation response element apical loop and motional correlations with the bulge by NMR, molecular dynamics, and mutagenesis. Publishing Authors By Initials

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Characterizing complex dynamics in the transactivation response element apical loop and motional correlations with the bulge by NMR, molecular dynamics, and mutagenesis. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Biophysical journal

VOLUME: 95

Page Numbers: 3906-15

Journal Abbreviation: Biophys. J.

ISSN: 1542-0086

DAY: 11

MONTH: 07

YEAR: 2008

Characterizing complex dynamics in the transactivation response element apical loop and motional correlations with the bulge by NMR, molecular dynamics, and mutagenesis. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 370626

Characterizing complex dynamics in the transactivation response element apical loop and motional correlations with the bulge by NMR, molecular dynamics, and mutagenesis. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Characterizing complex dynamics in the transactivation response element apical loop and motional correlations with the bulge by NMR, molecular dynamics, and mutagenesis. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Characterizing complex dynamics in the transactivation response element apical loop and motional correlations with the bulge by NMR, molecular dynamics, and mutagenesis.

AFFILIATION: Department of Chemistry and Biophysics, University of Michigan, Ann Arbor, Michigan 48109-1055, USA.

Country: United States

AGENCY: United States NIAID

GRANT: R01 AI066975-01

ACRONYM: AI

MEDLINETA: Biophys J

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Characterizing complex dynamics in the transactivation response element apical loop and motional correlations with the bulge by NMR, molecular dynamics, and mutagenesis Related Publications

• Bilateral hippocampal hyperintensities: a new finding in MR imaging of heat stroke.
• Characterizing complex dynamics in the transactivation response element apical loop and motional correlations with the bulge by NMR, molecular dynamics, and mutagenesis.
• Characterizing the relative orientation and dynamics of RNA A-form helices using NMR residual dipolar couplings.
• Dynamics of large elongated RNA by NMR carbon relaxation.
• Extending the NMR spatial resolution limit for RNA by motional couplings.
• Impact of static and dynamic A-form heterogeneity on the determination of RNA global structural dynamics using NMR residual dipolar couplings.
• In vitro effect of different non-steroidal anti-inflammatory drugs on human polymorphonuclear leukocyte activity measured by luminol-dependent chemiluminescence of the whole blood.
• NMR studies of RNA dynamics and structural plasticity using NMR residual dipolar couplings.
• 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 motions between equivalent RNA domains using magnetic field induced residual dipolar couplings: accounting for correlations between motions and alignment.
• Resolving fast and slow motions in the internal loop containing stem-loop 1 of HIV-1 that are modulated by Mg2+ binding: role in the kissing-duplex structural transition.
• Structural plasticity and Mg2+ binding properties of RNase P P4 from combined analysis of NMR residual dipolar couplings and motionally decoupled spin relaxation.
• Visualizing spatially correlated dynamics that directs RNA conformational transitions.