- Title
- The FOXP2 forkhead domain binds to a variety of DNA sequences with different rates and affinities
- Creator
- Webb, Helen, Steeb, Olga, Blane, Ashleigh, Rotherham, Lia, Aron, Shaun, Machanick, Philip, Dirr, Heinrich W, Fanucchi, Sylvia
- Subject
- To be catalogued
- Date
- 2017
- Type
- text
- Type
- article
- Identifier
- http://hdl.handle.net/10962/439326
- Identifier
- vital:73567
- Identifier
- https://doi.org/10.1093/jb/mvx003
- Description
- FOXP2 is a member of the P subfamily of FOX transcription factors, the DNA-binding domain of which is the winged helix forkhead domain (FHD). In this work we show that the FOXP2 FHD is able to bind to various DNA sequences, including a novel sequence identified in this work, with different affinities and rates as detected using surface plasmon resonance. Combining the experimental work with molecular docking, we show that high-affinity sequences remain bound to the protein for longer, form a greater number of interactions with the protein and induce a greater structural change in the protein than low-affinity sequences. We propose a binding model for the FOXP2 FHD that involves three types of binding sequence: low affinity sites which allow for rapid scanning of the genome by the protein in a partially unstructured state; moderate affinity sites which serve to locate the protein near target sites and high-affinity sites which secure the protein to the DNA and induce a conformational change necessary for functional binding and the possible initiation of downstream transcriptional events.
- Format
- 9 pages, pdf
- Language
- English
- Relation
- Oxford University Press, Webb, H., Steeb, O., Blane, A., Rotherham, L., Aron, S., Machanick, P., Dirr, H. and Fanucchi, S., 2017. The FOXP2 forkhead domain binds to a variety of DNA sequences with different rates and affinities. The journal of biochemistry, 162(1), pp.45-54, Oxford University Press volume 162 number 1 45 54 2017
- Rights
- Publisher
- Rights
- Use of this resource is governed by the terms and conditions of the Oxford Academic Journals Open Access Policy Statement (https://academic.oup.com/journals/pages/open_access)
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