RT Journal Article
SR Electronic
T1 A new perspective on the evolution of the interaction between the Vg/VGLL1-3 proteins and the TEAD transcription factors
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.05.21.107789
DO 10.1101/2020.05.21.107789
A1 Yannick Mesrouze
A1 Gustavo Aguilar
A1 Fedir Bokhovchuk
A1 Typhaine Martin
A1 Clara Delaunay
A1 Frédéric Villard
A1 Marco Meyerhofer
A1 Catherine Zimmermann
A1 Patrizia Fontana
A1 Roman Wille
A1 Thomas Vorherr
A1 Dirk Erdmann
A1 Pascal Furet
A1 Clemens Scheufler
A1 Tobias Schmelzle
A1 Markus Affolter
A1 Patrick Chène
YR 2020
UL http://biorxiv.org/content/early/2020/05/22/2020.05.21.107789.abstract
AB 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 and in vivo function. 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.Competing Interest StatementThe authors have declared no competing interest.