title: The surprising features of the TEAD4-Vgll1 protein-protein interaction.
abstract: The Hippo signaling pathway, which controls organ size in animals, is altered in various human cancers. The TEAD transcription factors, the most downstream elements in this pathway, are regulated by different cofactors, such as the Vgll (vestigial-like) proteins. Having studied the interaction between Vgll1-derived peptides and human TEAD4, we show that, although it lacks a key secondary structure element required for tight binding by two other TEAD cofactors (YAP and TAZ), Vgll1-derived peptides bind to TEAD with nanomolar affinity. We identify a β-strand:loop:α-helix motif as the minimal Vgll binding site. Finally, we reveal an unexpected difference between mouse and human Vgll1-derived peptides.
authors: Disease Area Oncology, Novartis Institutes for Biomedical Research, 141 Klybeckstrasse, 4057 Basel (Switzerland).
authors: Yannick
authors: Y
authors: Mesrouze
authors: Jean Christophe
authors: JC
authors: Hau
authors: Dirk
authors: D
authors: Erdmann
authors: Catherine
authors: C
authors: Zimmermann
authors: Patrizia
authors: P
authors: Fontana
authors: Tobias
authors: T
authors: Schmelzle
authors: Patrick
authors: P
authors: Chène
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D010455:Peptides; D011994:Recombinant Proteins; D000091262:TEA Domain Transcription Factors; C486309:TEAD4 protein, human; D014157:Transcription Factors; C470573:VGLL2 protein, human
keywords: Hippo pathway; TAZ; TEAD; Vgll proteins; YAP; peptides; protein-protein interactions