The FOXP2 forkhead domain binds to a variety of DNA sequences with different rates and affinities. (19th January 2017)

• Record Type: Journal Article
• Authors: Webb, Helen; Steeb, Olga; Blane, Ashleigh; Rotherham, Lia; Aron, Shaun; Machanick, Philip; Dirr, Heini; Fanucchi, Sylvia
• Is Part Of: Journal of biochemistry. Volume 162:Number 1(2017:Jul.)
• Page Start: 45
• Page End: 54
• Publication Date: 2017-01-19
• Subjects: binding affinity -- DNA-protein interactions -- FOXP2 -- sequence specificity -- transcription factor; Biochemistry -- Periodicals; Biochemistry -- Periodicals; Electronic journals; 572.05
• DOI: 10.1093/jb/mvx003
• Languages: English
• ISSNs: 0021-924X

Abstract

Abstract: 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.