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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / chemistry*
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Adaptor Proteins, Signal Transducing / metabolism
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Amino Acid Sequence
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Binding Sites
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / metabolism
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Humans
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Models, Molecular
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Molecular Sequence Data
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Nuclear Proteins / chemistry*
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Nuclear Proteins / metabolism
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Phosphoproteins / chemistry*
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Phosphoproteins / metabolism
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Protein Conformation
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Sequence Alignment
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TEA Domain Transcription Factors
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Trans-Activators / chemistry*
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Trans-Activators / metabolism
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Transcription Factors / chemistry*
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Transcription Factors / metabolism
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YAP-Signaling Proteins
Substances
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Adaptor Proteins, Signal Transducing
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DNA-Binding Proteins
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Nuclear Proteins
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Phosphoproteins
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TEA Domain Transcription Factors
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TEAD1 protein, human
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Trans-Activators
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Transcription Factors
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YAP-Signaling Proteins
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YAP1 protein, human