Identification of FAM181A and FAM181B as new interactors with the TEAD transcription factors

Bokhovchuk, Fedir; Mesrouze, Yannick; Delaunay, Clara; Martin, Typhaine; Villard, Frédéric; Meyerhofer, Marco; Fontana, Patrizia; Zimmermann, Catherine; Erdmann, Dirk; Furet, Pascal; Scheufler, Clemens; Schmelzle, Tobias; Chêne, Patrick

doi:10.1002/pro.3775

Cited by 27 publications

(45 citation statements)

References 40 publications

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“…We also repeatedly observed that the expression levels of FLAG-tagged VGLL2 were significantly higher in co-transfection experiments performed with TEAD4 proteins (Fig 4). In contrast to our previously reported observations for FAM181A (Bokhovchuk, Mesrouze et al, 2020), this effect happened with wild-type and mutant forms of TEAD4 and VGLL2, suggesting a the formation of a complex formation between these two proteins. This is presumably mediated through the interactions taking place at the β-strand:αhelix binding site, which are unaffected by the Asp272Ala TEAD4 or the deletion of the Ω-loop and may enhance the stability of co-overexpressed VGLL2 in this experimental setting.…”

Section: Presence Of An ω-Loop In Other Proteins Of the Vg/vgll1-3 Sucontrasting

confidence: 99%

“…At the end of the simulation, the linker region converged towards a loop conformation with no regular secondary structure that appeared stabilized by an aromatic stacking interaction between residues Tyr115 VGLL2 and Phe196 VGLL2 . All other cellular biology tools and methods, namely TEAD4 constructs and coimmunoprecipitations, were essentially as described previously (Bokhovchuk et al, 2020, Mesrouze et al, 2017a. NGS-PBT for 1 h. Samples were then incubated in primary antibody diluted in blocking solution over-night.…”

Section: Cloning Expression and Purification Of The Proteins For Thementioning

confidence: 99%

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A new perspective on the evolution of the interaction between the Vg/VGLL1-3 proteins and the TEAD transcription factors

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Bokhovchuk

et al. 2020

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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. elucidation of the structures of the YAP:TEAD (Chen, Chan et al., 2010, Li, Zhao et al., 2010 and of the VGLL1:TEAD (Pobbati, Chan et al., 2012) complexes has shed some light on how these proteins bind to TEAD. The TEAD-binding domain of YAP is formed of a β-strand:αhelix:Ω-loop motif while the TEAD-binding domain of VGLL1 contains only a β-strand:αhelix motif, known as TONDU domain, which binds to TEAD in a fashion similar to the βstrand:α-helix region of YAP ( Fig S1) (Li et al., 2010). The residues present in the TONDU domain of VGLL1 are well-conserved amongst the members of the Vg/VGLL1-3 family (Vg, vestigial, Drosophila homolog of VGLL1-3) (Simon, Faucheux et al., 2016) and no other regions of these proteins outside this motif have so far been reported to play a direct role in the interaction with TEAD proteins. Therefore, the main structural difference between the TEADbinding domain of these two cofactor families is the presence of an Ω-loop in the Yki/YAP proteins (Yki, Yorkie, Drosophila homolog of YAP), but not in the Vg/VGLL1-3 proteins.However, we made an observation which suggests that some members of the Vg/VGLL1-3 family may also possess an Ω-loop in their TEAD-binding domain. We identified a region in the amino acid sequence of the Vg protein from Drosophila melanogaster, residues 323-334 (Vg 323-334 ), which has a strong homology with the Ω-loop of YAP and is separated from the TONDU domain (Vg 288-311 ) by a similar number of residues compared with the Ω-loop from the β-strand:α-helix region in YAP ( Fig 1A). This unexpected finding, which suggests that Vg contains an Ω-loop, echoes earlier findings. Simmonds et al. have mapped the Sd-binding domain of Vg (Sd, Scalloped, Drosophila homolog of human TEAD) to Vg 279-335 , which contains not only the TONDU domain but also the putative Ω-loop, Vg 323-334 (Simmonds, Liu et al., 1998). However, these authors did not conduct experiments with shorter fragments to determine whether the entire Vg 279-335 is required for efficient binding to Sd. In their study of the ladybird beetl...

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Section: Presence Of An ω-Loop In Other Proteins Of the Vg/vgll1-3 Sucontrasting

confidence: 99%

Section: Cloning Expression and Purification Of The Proteins For Thementioning

confidence: 99%

A new perspective on the evolution of the interaction between the Vg/VGLL1-3 proteins and the TEAD transcription factors

Mesrouze

Aguilar

Bokhovchuk

et al. 2020

Preprint

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“…The pcDNA3.1 Hygro-DEST_VGLL2_Ω_loop mutant was generated by use of the QuikChange Lightning Site-Directed Mutagenesis kit (Stratagene, San Diego, CA), with oligo 5′ CCC TTG GAG AGA CTG CAG CTT CTA TCA GGC TCC TGT GCC 3′ (removing amino acid positions 134–149) and the sequence of resulting cDNA clones verified. All other cellular biology tools and methods, namely TEAD4 constructs and co-immunoprecipitations, were essentially as described previously 30 , 50 . The inter-experimental reproducibility across the co-IP experiments appeared less robust in the wild-type HEK293FT (i.e.…”

Section: Methodsmentioning

confidence: 99%

A new perspective on the interaction between the Vg/VGLL1-3 proteins and the TEAD transcription factors

Mesrouze

Aguilar

Bokhovchuk

et al. 2020

Sci Rep

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“…Several residues of the Ω‐loop region are well conserved (Figures 1c and 2). Zhang et al have suggested that Val84 Hs at the N‐terminus of the Ω‐loop has a shielding effect on the folding of this region 24 and the presence of this residue dramatically increases the affinity of peptides mimicking the Ω‐loop of YAP 23 . Val84 Hs is often replaced by a leucine and in some cases by an isoleucine or a lysine.…”

Section: Resultsmentioning

confidence: 99%

“…This residue is quite well conserved, but in a few sequences it is replaced by a tryptophan. It has been shown that the presence of a larger aromatic residue at position‐96 Hs (e.g., 1‐naphtylalanine) enhances the affinity of YAP 30 and that FAM181A, which also binds to TEAD via an Ω‐loop, contains a tryptophan at this position 23 . Phe96 Hs also makes a π‐cation interaction with Arg87 Hs , and this interaction is thought to contribute to the stabilization of the bound Ω‐loop (Figure 1c).…”

Section: Resultsmentioning

confidence: 99%

Study of the TEAD‐binding domain of the YAP protein from animal species

et al. 2020

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The Hippo signaling pathway, which plays a central role in the control of organ size in animals, is well conserved in metazoans. The most downstream elements of this pathway are the TEAD transcription factors that are regulated by their association with the transcriptional coactivator YAP. Therefore, the creation of the binding interface that ensures the formation of the YAP:TEAD complex is a critical molecular recognition event essential for the development/survival of many living organisms. In this report, using the available structural information on the YAP:TEAD complex, we study the TEADbinding domain of YAP from different animal species. This analysis of more than 400 amino acid sequences reveals that the residues from YAP involved in the formation of the two main contact regions with TEAD are very well conserved. Therefore, the binding interface between YAP and TEAD, as found in humans, probably appeared at an early evolutionary stage in metazoans. We find that, in contrast to most other animal species, several Actinopterygii species possess YAP variants with a different TEAD-binding domain. However, these variants bind to TEAD with a similar affinity. Our studies show that the protein identified as a YAP homolog in Caenorhabditis elegans does not contain the TEAD-binding domain found in YAP of other metazoans. Finally, we do not identify in non-metazoan species, amino acid sequences containing both a TEAD-binding domain, as in metazoan YAP, and WW domain(s).

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Identification of FAM181A and FAM181B as new interactors with the TEAD transcription factors

Cited by 27 publications

References 40 publications

A new perspective on the evolution of the interaction between the Vg/VGLL1-3 proteins and the TEAD transcription factors

A new perspective on the evolution of the interaction between the Vg/VGLL1-3 proteins and the TEAD transcription factors

A new perspective on the interaction between the Vg/VGLL1-3 proteins and the TEAD transcription factors

Study of the TEAD‐binding domain of the YAP protein from animal species

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