Evidence that Electrostatic Interactions Dictate the Ligand‐Induced Arrest of RNA Global Flexibility

Pitt, Stephen W.; Zhang, Qi; Patel, Dinshaw J.; Al‐Hashimi, Hashim M.

doi:10.1002/anie.200500075

Cited by 31 publications

(31 citation statements)

References 37 publications

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“…128,129,[140][141][142][143] Figure 11 shows some of these TAR conformational transitions as visualized through application of an order tensor analysis of RDCs. 85,[94][95][96] Interestingly, one finds that molecules that contribute a larger number of cationic groups tend to stabilize more linear and rigid TAR conformations (Figure 11), in analogy to the trend observed when adding metals (Mg 21 ) as discussed earlier.…”

Section: Molecular Recognitionsupporting

confidence: 67%

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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Section: Molecular Recognitionsupporting

confidence: 67%

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

et al. 2007

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“…Overall, our results are remarkably similar to those that have been previously measured for TAR (2,4,6,19,20,(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46). Both RNAs have similar average interhelical bend angles (~43 (FS) and~47 (TAR) (36)), exhibit fast timescale nucleotide dynamics in their trinucleotide bulge and loop regions (27,42,44), and display markedly anisotropic helical motions (43) that are quenched by physiological concentrations of magnesium (37,101).…”

Section: Discussionsupporting

confidence: 89%

“…It is not yet clear whether the large amplitude dynamic motions of TAR (19,36) and their modulation by counterions (3,(37)(38)(39)(40) are sequence-specific or reflect a more general feature of trinucleotide bulges. Changing the sequence identity of a Watson-Crick basepair flanking the TAR bulge from A-U to a more stable G-C significantly diminishes the amplitude of interhelical motions (17), supporting the idea of sequence-dependent bulge dynamics.…”

Section: Introductionmentioning

confidence: 99%

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Dynamic Motions of the HIV-1 Frameshift Site RNA

Mouzakis

Dethoff

Tonelli

et al. 2015

Biophysical Journal

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The HIV-1 frameshift site (FS) plays a critical role in viral replication. During translation, the HIV-1 FS transitions from a 3-helix to a 2-helix junction RNA secondary structure. The 2-helix junction structure contains a GGA bulge, and purine-rich bulges are common motifs in RNA secondary structure. Here, we investigate the dynamics of the HIV-1 FS 2-helix junction RNA. Interhelical motions were studied under different ionic conditions using NMR order tensor analysis of residual dipolar couplings. In 150 mM potassium, the RNA adopts a 43°(±4°) interhelical bend angle (β) and displays large amplitude, anisotropic interhelical motions characterized by a 0.52(±0.04) internal generalized degree of order (GDOint) and distinct order tensor asymmetries for its two helices (η = 0.26(±0.04) and 0.5(±0.1)). These motions are effectively quenched by addition of 2 mM magnesium (GDOint = 0.87(±0.06)), which promotes a near-coaxial conformation (β = 15°(±6°)) of the two helices. Base stacking in the bulge was investigated using the fluorescent purine analog 2-aminopurine. These results indicate that magnesium stabilizes extrahelical conformations of the bulge nucleotides, thereby promoting coaxial stacking of helices. These results are highly similar to previous studies of the HIV transactivation response RNA, despite a complete lack of sequence similarity between the two RNAs. Thus, the conformational space of these RNAs is largely determined by the topology of their interhelical junctions.

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“…1B). The local structure of these domains has previously been validated using RDCs measured in free TAR [43] and for TAR bound to four distinct ligands that target the bulge and neighboring residues without affecting the remaining local helical structure [44][45][46]. The 108 RDCs belonging to TAR residues that coincide with those of TAR4312 fit (using SVD [41]) the above domain structures with an overall rmsd (normalized to reflect the TAR4312 degree of order) of 1.5 Hz (Fig.…”

Section: Resultsmentioning

confidence: 95%

Insight into the CSA tensors of nucleobase carbons in RNA polynucleotides from solution measurements of residual CSA: Towards new long-range orientational constraints

Hansen

Al‐Hashimi

2006

Journal of Magnetic Resonance

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Evidence that Electrostatic Interactions Dictate the Ligand‐Induced Arrest of RNA Global Flexibility

Cited by 31 publications

References 37 publications

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

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

Dynamic Motions of the HIV-1 Frameshift Site RNA

Insight into the CSA tensors of nucleobase carbons in RNA polynucleotides from solution measurements of residual CSA: Towards new long-range orientational constraints

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