A new perspective on the interaction between the Vg/VGLL1-3 proteins and the TEAD transcription factors.
Animals
Binding Sites
DNA-Binding Proteins
/ chemistry
Drosophila
HEK293 Cells
Humans
Inhibitory Concentration 50
Kinetics
Models, Molecular
Muscle Proteins
/ chemistry
Mutation
Nuclear Proteins
/ chemistry
Protein Binding
Protein Domains
TEA Domain Transcription Factors
Transcription Factors
/ chemistry
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
15 10 2020
15 10 2020
Historique:
received:
10
06
2020
accepted:
30
09
2020
entrez:
16
10
2020
pubmed:
17
10
2020
medline:
10
3
2021
Statut:
epublish
Résumé
The most downstream elements of the Hippo pathway, the TEAD transcription factors, are regulated by several cofactors, such as Vg/VGLL1-3. Earlier findings on human VGLL1 and here on human VGLL3 show that these proteins interact with TEAD via a conserved amino acid motif called the TONDU domain. Surprisingly, our studies reveal that the TEAD-binding domain of Drosophila Vg and of human VGLL2 is more complex and contains an additional structural element, an Ω-loop, that contributes to TEAD binding. To explain this unexpected structural difference between proteins from the same family, we propose that, after the genome-wide duplications at the origin of vertebrates, the Ω-loop present in an ancestral VGLL gene has been lost in some VGLL variants. These findings illustrate how structural and functional constraints can guide the evolution of transcriptional cofactors to preserve their ability to compete with other cofactors for binding to transcription factors.
Identifiants
pubmed: 33060790
doi: 10.1038/s41598-020-74584-x
pii: 10.1038/s41598-020-74584-x
pmc: PMC7566471
doi:
Substances chimiques
DNA-Binding Proteins
0
Muscle Proteins
0
Nuclear Proteins
0
TEA Domain Transcription Factors
0
TEAD1 protein, human
0
Transcription Factors
0
VGLL1 protein, human
0
VGLL2 protein, human
0
VGLL3 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
17442Références
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