An Alternating Sheared AA Pair and Elements of Stability for a Single Sheared Purine-Purine Pair Flanked by Sheared GA Pairs in RNA<sup>,</sup>

Chen, G.; Kennedy, Scott D.; Qiao, Jing; Krugh, Thomas R.; Turner, Douglas H.

doi:10.1021/bi0524464

Cited by 28 publications

(48 citation statements)

References 67 publications

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“…In the minor conformation: (1) the iG6H1′ proton is shifted 1.27 ppm upfield relative to the major conformation ( Figure S1 and Table S4), consistent with the shift induced by the adenine ring of a sheared GA pair, as observed for iC6H1′ in (GCiGGAiCGCA) 2 and other structures; 8,14,64 (2) the G4 imino proton is shifted upfield to 9.8 ppm (Figure 2, 3, and Table S4), consistent with an imino proton not involved in a hydrogen bond; and (3) the G4 ribose ring is observed to exist partially in the C2′-endo conformation ( Figure S4), consistent with the observation that in several structures involving thermodynamically less stable sheared GA pairs, the G ribose is found to be in the C2′-endo conformation. 11,14,15,60,64 It cannot be determined, however, whether the C2′-endo pucker occurs when the GA pair is in the major or minor conformation or both.…”

Section: Discussionsupporting

confidence: 81%

Stacking Effects on Local Structure in RNA: Changes in the Structure of Tandem GA Pairs when Flanking GC Pairs Are Replaced by isoG−isoC Pairs

et al. 2007

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The Watson-Crick like iGiC pair, with the amino and carbonyl groups transposed relative to the Watson-Crick GC pair, provides an expanded alphabet for understanding interactions that shape nucleic acid structure. Here, thermodynamic stabilities of tandem GA pairs flanked by iGiC pairs are reported along with the NMR structures of the the RNA self-complementary duplexes (GCiGGAiCGCA) 2 and (GGiCGAiGCCA) 2 . A sheared GA pairing forms in (GCiGGAiCGCA) 2 and an imino GA pairing forms in (GGiCGAiGCCA) 2 . The structures contrast with the formation of tandem imino and sheared GA pairs flanked by GC pairs in the RNA self-complementary duplexes (GCGGACGC) 2 and (GGCGAGCC) 2 , respectively. In both iGiC duplexes, WatsonCrick like hydrogen bonds are formed between iG and iC, and iGiC substitutions result in less favorable loop stability. The results provide benchmarks for testing computations of molecular interactions that shape RNA three-dimensional structure.

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Section: Discussionsupporting

confidence: 81%

Stacking Effects on Local Structure in RNA: Changes in the Structure of Tandem GA Pairs when Flanking GC Pairs Are Replaced by isoG−isoC Pairs

et al. 2007

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“…24 The Altona & Sunderlingam 70 convention was used to measure the sugar pucker along the MD trajectories of the major and minor conformations. The NMR results indicate the nucleotides have C3' endo sugar puckers with angles ranging from 0 to 36°.…”

Section: Resultsmentioning

confidence: 99%

“…24 The dangling ends (unpaired U and purine), added to stabilize the structures for NMR, were removed for these calculations. Both structures have the same covalent structure and consist of 587 atoms.…”

Section: Methodsmentioning

confidence: 99%

“…23 The NMR data obtained by Chen et al for the duplex contained NOEs that were inconsistent with a single structure. 24 The NMR data was divided into two sets of NOE and dihedral angle restraints, based on a prior well-determined structure 25 that were separately used to model structures for the major (Protein Data Bank, PDB, accession #: 2DD2) and minor (pdb: 2DD3) conformations. 24 Estimates of chemical shift differences of the H2 of adenine-5 between major and minor forms suggest an exchange rate of at least 435 s −1 while line widths suggest higher rates ranging from 20,000 to 65,000 s −1 .…”

Section: Introductionmentioning

confidence: 99%

“…24 The NMR data was divided into two sets of NOE and dihedral angle restraints, based on a prior well-determined structure 25 that were separately used to model structures for the major (Protein Data Bank, PDB, accession #: 2DD2) and minor (pdb: 2DD3) conformations. 24 Estimates of chemical shift differences of the H2 of adenine-5 between major and minor forms suggest an exchange rate of at least 435 s −1 while line widths suggest higher rates ranging from 20,000 to 65,000 s −1 . 24 The observed chemical shifts of A5 and A15 H2 protons suggested that the major conformation is 0.5 to 1.3 kcal/mol more stable than the minor conformation at 30 °C.…”

Section: Introductionmentioning

confidence: 99%

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Molecular Mechanics Investigation of an Adenine–Adenine Non-Canonical Pair Conformational Change

Nostrand

Kennedy

Turner

et al. 2011

J. Chem. Theory Comput.

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Conformational changes are important in RNA for binding and catalysis and understanding these changes is important for understanding how RNA functions. Computational techniques using all-atom molecular models can be used to characterize conformational changes in RNA. These techniques are applied to an RNA conformational change involving a single base pair within a nine base pair RNA duplex. The Adenine-Adenine (AA) non-canonical pair in the sequence 5'GGUGAAGGCU3' paired with 3'PCCGAAGCCG5', where P is Purine, undergoes conformational exchange between two conformations on the timescale of tens of microseconds, as demonstrated in a previous NMR solution structure [Chen, G., et al., Biochemistry, 2006. 45: 6889–903]. The more populated, major, conformation was estimated to be 0.5 to 1.3 kcal/mol more stable at 30 °C than the less populated, minor, conformation. Both conformations are trans-Hoogsteen/sugar edge pairs, where the interacting edges on the adenines change with the conformational change. Targeted Molecular Dynamics (TMD) and Nudged Elastic Band (NEB) were used to model the pathway between the major and minor conformations using the AMBER software package. The adenines were predicted to change conformation via intermediates in which they are stacked as opposed to hydrogen-bonded. The predicted pathways can be described by an improper dihedral angle reaction coordinate. Umbrella sampling along the reaction coordinate was performed to model the free energy profile for the conformational change using a total of 1800 ns of sampling. Although the barrier height between the major and minor conformations was reasonable, the free energy difference between the major and minor conformations was the opposite of that expected based on the NMR experiments. Variations in the force field applied did not improve the misrepresentation of the free energies of the major and minor conformations. As an alternative, the Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) approximation was applied to predict free energy differences between the two conformations using a total of 800 ns of sampling. MM-PBSA also incorrectly predicted the major conformation to be higher in free energy than the minor conformation.

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A U⋅U Pair‐to‐U⋅C Pair Mutation‐Induced RNA Native Structure Destabilisation and Stretching‐Force‐Induced RNA Misfolding

et al. 2015

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Little is known about how a non‐Watson–Crick pair affects the RNA folding dynamics. We studied the effects of a U⋅U‐to‐U⋅C pair mutation on the folding of a hairpin in human telomerase RNA. The ensemble thermal melting of the hairpins shows an on‐pathway intermediate with the disruption of the internal loop structure containing the U⋅U/U⋅C pairs. By using optical tweezers, we applied a stretching force on the terminal ends of the hairpins to probe directly the non‐nearest‐neighbour effects upon the mutations. The single U⋅U to U⋅C mutations are observed to 1) lower the mechanical unfolding force by approximately 1 picoNewton (pN) per mutation without affecting the unfolding reaction transition‐state position (thus suggesting that removing a single hydrogen bond affects the structural dynamics at least two base pairs away), 2) result in more frequent misfolding into a small hairpin at approximately 10 pN and 3) shift the folding reaction transition‐state position towards the native hairpin structure and slightly increase the mechanical folding kinetics (thus suggesting that untrapping from the misfolded state is not the rate‐limiting step).

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An Alternating Sheared AA Pair and Elements of Stability for a Single Sheared Purine-Purine Pair Flanked by Sheared GA Pairs in RNA^,

Cited by 28 publications

References 67 publications

Stacking Effects on Local Structure in RNA: Changes in the Structure of Tandem GA Pairs when Flanking GC Pairs Are Replaced by isoG−isoC Pairs

Stacking Effects on Local Structure in RNA: Changes in the Structure of Tandem GA Pairs when Flanking GC Pairs Are Replaced by isoG−isoC Pairs

Molecular Mechanics Investigation of an Adenine–Adenine Non-Canonical Pair Conformational Change

A U⋅U Pair‐to‐U⋅C Pair Mutation‐Induced RNA Native Structure Destabilisation and Stretching‐Force‐Induced RNA Misfolding

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An Alternating Sheared AA Pair and Elements of Stability for a Single Sheared Purine-Purine Pair Flanked by Sheared GA Pairs in RNA,

Cited by 28 publications

References 67 publications

Stacking Effects on Local Structure in RNA: Changes in the Structure of Tandem GA Pairs when Flanking GC Pairs Are Replaced by isoG−isoC Pairs

Stacking Effects on Local Structure in RNA: Changes in the Structure of Tandem GA Pairs when Flanking GC Pairs Are Replaced by isoG−isoC Pairs

Molecular Mechanics Investigation of an Adenine–Adenine Non-Canonical Pair Conformational Change

A U⋅U Pair‐to‐U⋅C Pair Mutation‐Induced RNA Native Structure Destabilisation and Stretching‐Force‐Induced RNA Misfolding

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An Alternating Sheared AA Pair and Elements of Stability for a Single Sheared Purine-Purine Pair Flanked by Sheared GA Pairs in RNA^,