Single-molecule conformational dynamics of a transcription factor reveals a continuum of binding modes controlling association and dissociation
| dc.citation.firstpage | 11211 | |
| dc.citation.issueNumber | 19 | |
| dc.citation.journalTitle | Nucleic Acids Research | |
| dc.citation.lastpage | 11223 | |
| dc.citation.volumeNumber | 49 | |
| dc.contributor.author | Chen, Wei | |
| dc.contributor.author | Lu, Wei | |
| dc.contributor.author | Wolynes, Peter G | |
| dc.contributor.author | Komives, Elizabeth A | |
| dc.contributor.org | Center for Theoretical Biological Physics | |
| dc.date.accessioned | 2021-12-15T22:10:20Z | |
| dc.date.available | 2021-12-15T22:10:20Z | |
| dc.date.issued | 2021 | |
| dc.description.abstract | Binding and unbinding of transcription factors to DNA are kinetically controlled to regulate the transcriptional outcome. Control of the release of the transcription factor NF-κB from DNA is achieved through accelerated dissociation by the inhibitor protein IκBα. Using single-molecule FRET, we observed a continuum of conformations of NF-κB in free and DNA-bound states interconverting on the subseconds to minutes timescale, comparable to in vivo binding on the seconds timescale, suggesting that structural dynamics directly control binding kinetics. Much of the DNA-bound NF-κB is partially bound, allowing IκBα invasion to facilitate DNA dissociation. IκBα induces a locked conformation where the DNA-binding domains of NF-κB are too far apart to bind DNA, whereas a loss-of-function IκBα mutant retains the NF-κB conformational ensemble. Overall, our results suggest a novel mechanism with a continuum of binding modes for controlling association and dissociation of transcription factors. | |
| dc.identifier.citation | Chen, Wei, Lu, Wei, Wolynes, Peter G, et al.. "Single-molecule conformational dynamics of a transcription factor reveals a continuum of binding modes controlling association and dissociation." <i>Nucleic Acids Research,</i> 49, no. 19 (2021) Oxford University Press: 11211-11223. https://doi.org/10.1093/nar/gkab874. | |
| dc.identifier.digital | gkab874 | |
| dc.identifier.doi | https://doi.org/10.1093/nar/gkab874 | |
| dc.identifier.uri | https://hdl.handle.net/1911/111794 | |
| dc.language.iso | eng | |
| dc.publisher | Oxford University Press | |
| dc.rights | This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. | |
| dc.rights.uri | https://creativecommons.org/licenses/by-nc/4.0/ | |
| dc.title | Single-molecule conformational dynamics of a transcription factor reveals a continuum of binding modes controlling association and dissociation | |
| dc.type | Journal article | |
| dc.type.dcmi | Text | |
| dc.type.publication | publisher version |
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