ArticleThe Journal of biological chemistry2011
Constitutive regulatory activity of an evolutionarily excluded riboswitch variant.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- A structural intermediate pre-organizes the add adenine riboswitch for ligand recognition.Nucleic acids research · 2021Article
- Ligand recognition and helical stacking formation are intimately linked in the SAM-I riboswitch regulatory mechanism.RNA (New York, N.Y.) · 2017Article
- Fluorescence-Based Strategies to Investigate the Structure and Dynamics of Aptamer-Ligand Complexes.Frontiers in chemistry · 2016Review
- A kissing loop is important for btuB riboswitch ligand sensing and regulatory control.The Journal of biological chemistry · 2015Article
- Article
- Native purification and labeling of RNA for single molecule fluorescence studies.Methods in molecular biology (Clifton, N.J.) · 2015Article
- Ligand binding by the tandem glycine riboswitch depends on aptamer dimerization but not double ligand occupancy.RNA (New York, N.Y.) · 2014Article
- Single-molecule studies of riboswitch folding.Biochimica et biophysica acta · 2014Review
- Fluorescence monitoring of riboswitch transcription regulation using a dual molecular beacon assay.Nucleic acids research · 2013Article
- Single-molecule chemical denaturation of riboswitches.Nucleic acids research · 2013Article
- Evolutionary evidence for alternative structure in RNA sequence co-variation.PLoS computational biology · 2013Article
- Molecular recognition and function of riboswitches.Current opinion in structural biology · 2012Review
- Allosteric tertiary interactions preorganize the c-di-GMP riboswitch and accelerate ligand binding.ACS chemical biology · 2012Article
- Conformational heterogeneity of the SAM-I riboswitch transcriptional ON state: a chaperone-like role for S-adenosyl methionine.Journal of molecular biology · 2012Article
- Metabolite recognition principles and molecular mechanisms underlying riboswitch function.Annual review of biophysics · 2012Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
The exquisite specificity of the adenine-responsive riboswitch toward its cognate metabolite has been shown to arise from the formation of a Watson-Crick interaction between the adenine ligand and residue U65. A recent crystal structure of a U65C adenine aptamer variant has provided a rationale for the phylogenetic conservation observed at position 39 for purine aptamers. The G39-C65 variant adopts a compact ligand-free structure in which G39 is accommodated by the ligand binding site and is base-paired to the cytosine at position 65. Here, we demonstrate using a combination of biochemical and biophysical techniques that the G39-C65 base pair not only severely impairs ligand binding but also disrupts the functioning of the riboswitch in vivo by constitutively activating gene expression. Folding studies using single-molecule FRET revealed that the G39-C65 variant displays a low level of dynamic heterogeneity, a feature reminiscent of ligand-bound wild-type complexes. A restricted conformational freedom together with an ability to significantly fold in monovalent ions are exclusive to the G39-C65 variant. This work provides a mechanistic framework to rationalize the evolutionary exclusion of certain nucleotide combinations in favor of sequences that preserve ligand binding and gene regulation functionalities.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.