Structural insights into the YAP and TEAD complex

  1. Ze Li1,2,5,
  2. Bin Zhao3,5,
  3. Ping Wang1,
  4. Fei Chen1,
  5. Zhenghong Dong1,
  6. Huirong Yang1,
  7. Kun-Liang Guan3,7 and
  8. Yanhui Xu1,2,4,6
  1. 1School of Life Sciences, Fudan University, Shanghai 200433, China;
  2. 2Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China;
  3. 3Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, California 92093, USA;
  4. 4Department of Pathology, Cancer Hospital, Fudan University, Shanghai 200032, China
    1. 5 These authors contributed equally to this work.

    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.

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