title: Structural insights into the YAP and TEAD complex.
abstract: The Yes-associated protein (YAP) transcriptional coactivator is a key regulator of organ size and a candidate human oncogene inhibited by the Hippo tumor suppressor pathway. The TEAD family of transcription factors binds directly to and mediates YAP-induced gene expression. Here we report the three-dimensional structure of the YAP (residues 50-171)-TEAD1 (residues 194-411) complex, in which YAP wraps around the globular structure of TEAD1 and forms extensive interactions via three highly conserved interfaces. Interface 3, including YAP residues 86-100, is most critical for complex formation. Our study reveals the biochemical nature of the YAP-TEAD interaction, and provides a basis for pharmacological intervention of YAP-TEAD hyperactivation in human diseases.
authors.affiliation: School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Ze
authors.initials: Z
authors.lastname: Li
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Dong
authors.forename: Huirong
authors.initials: H
authors.lastname: Yang
authors.forename: Kun-Liang
authors.initials: KL
authors.lastname: Guan
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Xu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D016415:Sequence Alignment; D000091262:TEA Domain Transcription Factors; D015534:Trans-Activators / Q000737:chemistry* / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D000091262:TEA Domain Transcription Factors; C057182:TEAD1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human