ArticleProceedings of the National Academy of Sciences of the United States of America2014
Direct observation of a transient ternary complex during IκBα-mediated dissociation of NF-κB from DNA.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 42 citations in OpenAlex.
- Article
- From molecular descriptions to cellular functions of intrinsically disordered protein regions.Biophysics reviews · 2024Review
- The multifunctional role of intrinsic disorder in NF-κB signaling.Biochemical Society transactions · 2023Review
- Site-specific incorporation of biophysical probes into NF-ĸB with non-canonical amino acids.Methods (San Diego, Calif.) · 2023Article
- Overexpression of IκB⍺ modulates NF-κB activation of inflammatory target gene expression.Frontiers in molecular biosciences · 2023Article
- A novel and atypical NF-KB pro-inflammatory program regulated by a CamKII-proteasome axis is involved in the early activation of Muller glia by high glucose.Cell & bioscience · 2022Article
- Single-molecule conformational dynamics of a transcription factor reveals a continuum of binding modes controlling association and dissociation.Nucleic acids research · 2021Article
- How to assess the structural dynamics of transcription factors by integrating sparse NMR and EPR constraints with molecular dynamics simulations.Computational and structural biotechnology journal · 2021Review
- How do DNA-bound proteins leave their binding sites? The role of facilitated dissociation.Current opinion in chemical biology · 2019Review
- Genome reading by the NF-κB transcription factors.Nucleic acids research · 2019Review
- Force-Dependent Facilitated Dissociation Can Generate Protein-DNA Catch Bonds.Biophysical journal · 2019Article
- Exclusivity and Compensation in NFκB Dimer Distributions and IκB Inhibition.Biochemistry · 2019Article
- Considering Abundance, Affinity, and Binding Site Availability in the NF-κB Target Selection Puzzle.Frontiers in immunology · 2019Review
- Prediction of the presence of a seventh ankyrin repeat in IκBε from homology modeling combined with hydrogen-deuterium exchange mass spectrometry (HDX-MS).Protein science : a publication of the Protein Society · 2018Article
- Hydrogen-deuterium exchange mass spectrometry reveals folding and allostery in protein-protein interactions.Methods (San Diego, Calif.) · 2018Review
- RelA-Containing NFκB Dimers Have Strikingly Different DNA-Binding Cavities in the Absence of DNA.Journal of molecular biology · 2018Article
- AT1 receptor blockage impairs NF-κB activation mediated by thyroid hormone in cardiomyocytes.Pflugers Archiv : European journal of physiology · 2018Article
- Modeling the therapeutic efficacy of NFκB synthetic decoy oligodeoxynucleotides (ODNs).BMC systems biology · 2018Article
- Stochastic resonances in a distributed genetic broadcasting system: the NFJournal of the Royal Society, Interface · 2018Article
- Stochastic dynamics of genetic broadcasting networks.Physical review. E · 2017Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
We previously demonstrated that IκBα markedly increases the dissociation rate of DNA from NF-κB. The mechanism of this process remained a puzzle because no ternary complex was observed, and structures show that the DNA and IκBα binding sites on NF-κB are overlapping. The kinetics of interaction of IκBα with NF-κB and its complex with DNA were analyzed by using stopped-flow experiments in which fluorescence changes in pyrene-labeled DNA or the native tryptophan in IκBα were monitored. Rate constants governing the individual steps in the reaction were obtained from analysis of the measured rate vs. concentration profiles. The NF-κB association with DNA is extremely rapid with a rate constant of 1.5 × 10(8) M(-1)⋅s(-1). The NF-κB-DNA complex dissociates with a rate constant of 0.41 s(-1), yielding a KD of 2.8 nM. When IκBα is added to the NF-κB-DNA complex, we observe the formation of a transient ternary complex in the first few milliseconds of the fluorescence trace, which rapidly rearranges to release DNA. The rate constant of this IκBα-mediated dissociation is nearly equal to the rate constant of association of IκBα with the NF-κB-DNA complex, showing that IκBα is optimized to repress transcription. The rate constants for the individual steps of a more folded mutant IκBα were also measured. This mutant associates with NF-κB more rapidly than wild-type IκBα, but it associates with the NF-κB-DNA complex more slowly and also is less efficient at mediating dissociation of the NF-κB-DNA complex.
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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.