Different Recognition of TEAD Transcription Factor by the Conserved B‐strand:loop:a–helix Motif of the TEAD Binding Site of YAP and VGLL1. Issue 11 (28th July 2016)

• Record Type: Journal Article
• Authors: Mesrouze, Yannick; Erdmann, Dirk; Fontana, Patrizia; Meyerhofer, Marco; Zimmermann, Catherine; Schmelzle, Tobias; Chène, Patrick
• Is Part Of: ChemistrySelect. Volume 1:Issue 11(2016)
• Page Start: 2993
• Page End: 2997
• Publication Date: 2016-07-28
• Subjects: YAP -- TEAD -- VGLL -- protein-protein interaction -- molecular recognition -- peptide; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.201600599
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: The TEAD (TEA/ATTS domain) transcription factors are regulated by various coactivator proteins. A β‐strand:loop:α‐helix motif is present at the TEAD binding site of all the coactivators crystallized so far. These motifs interact with the same area of TEAD, suggesting that the coactivators compete with each other in vivo to gain access to TEAD. The α‐helix, which shows marked interactions with TEAD, is the key element of the β‐strand:loop:α‐helix motif. A very large difference in potency (>40 fold) has been measured between the isolated mouse VGLL1 (vestigial‐like 1, mVGLL1) α‐helix and its human YAP (Yes‐associated protein, hYAP) equivalent. Elucidating the mechanisms at the origin of this difference should help in better understanding how these coactivators interact with TEAD. In this report, we show that the β‐strand:loop:α‐helix motif of hYAP and mVGLL1 are optimized in a very different manner suggesting a convergent evolution of these coactivators for binding to the TEAD transcription factors. Abstract : The coactivators YAP (green) and VGLL1 (blue) bind to the transcription factor TEAD (green) via a conserved α‐helix. Despite a high primary sequence homology and a similar binding mode at TEAD surface, these two α‐helices have large difference in affinity for TEAD and that they are optimized in a very different manner for binding to TEAD.