Unraveling the folding and dimerization properties of the human FoxP subfamily of transcription factors.
DNA-binding proteins
FoxP subfamily
domain swapping
folding mechanism
forkhead domain
protein-protein interactions
Journal
FEBS letters
ISSN: 1873-3468
Titre abrégé: FEBS Lett
Pays: England
ID NLM: 0155157
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
revised:
20
04
2023
received:
29
03
2023
accepted:
09
05
2023
medline:
23
10
2023
pubmed:
18
5
2023
entrez:
18
5
2023
Statut:
ppublish
Résumé
Human FoxP proteins share a highly conserved DNA-binding domain that dimerizes via three-dimensional domain swapping, although showing varying oligomerization propensities among its members. Here, we present an experimental and computational characterization of all human FoxP proteins to unravel how their amino acid substitutions impact their folding and dimerization mechanism. We solved the crystal structure of the forkhead domain of FoxP4 to then perform a comparison across all members, finding that their sequence changes impact not only the structural heterogeneity of their forkhead domains but also the protein-protein association energy barrier. Lastly, we demonstrate that the accumulation of a monomeric intermediate is an oligomerization-dependent feature rather than a common aspect of monomers and dimers in this protein subfamily.
Identifiants
pubmed: 37199668
doi: 10.1002/1873-3468.14665
doi:
Substances chimiques
Transcription Factors
0
Repressor Proteins
0
Forkhead Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1894-1905Informations de copyright
© 2023 Federation of European Biochemical Societies.
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