DNA facilitates heterodimerization between human transcription factors FoxP1 and FoxP2 by increasing their conformational flexibility.
Biochemistry
Molecular biology
Structural biology
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
21 Jul 2023
21 Jul 2023
Historique:
received:
03
10
2022
revised:
15
05
2023
accepted:
20
06
2023
medline:
24
7
2023
pubmed:
24
7
2023
entrez:
24
7
2023
Statut:
epublish
Résumé
Transcription factors regulate gene expression by binding to DNA. They have disordered regions and specific DNA-binding domains. Binding to DNA causes structural changes, including folding and interactions with other molecules. The FoxP subfamily of transcription factors in humans is unique because they can form heterotypic interactions without DNA. However, it is unclear how they form heterodimers and how DNA binding affects their function. We used computational and experimental methods to study the structural changes in FoxP1's DNA-binding domain when it forms a heterodimer with FoxP2. We found that FoxP1 has complex and diverse conformational dynamics, transitioning between compact and extended states. Surprisingly, DNA binding increases the flexibility of FoxP1, contrary to the typical folding-upon-binding mechanism. In addition, we observed a 3-fold increase in the rate of heterodimerization after FoxP1 binds to DNA. These findings emphasize the importance of structural flexibility in promoting heterodimerization to form transcriptional complexes.
Identifiants
pubmed: 37485372
doi: 10.1016/j.isci.2023.107228
pii: S2589-0042(23)01305-6
pmc: PMC10362293
doi:
Types de publication
Journal Article
Langues
eng
Pagination
107228Informations de copyright
© 2023 The Authors.
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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