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PMID: 20123905 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Structural insights into the YAP and TEAD complex.

Genes & development ·Vol. 24 ·No. 3 ·2010-02-01 ·Pages 235-40

Li Z, Zhao B, Wang P, Chen F, Dong Z, Yang H, Guan KL, Xu Y

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.

MeSH Terms
Adaptor Proteins, Signal Transducing/chemistry,metabolism Amino Acid Sequence Binding Sites DNA-Binding Proteins/chemistry,metabolism Humans Models, Molecular Molecular Sequence Data Nuclear Proteins/chemistry,metabolism Phosphoproteins/chemistry,metabolism Protein Conformation Sequence Alignment TEA Domain Transcription Factors Trans-Activators/chemistry,metabolism Transcription Factors/chemistry,metabolism YAP-Signaling Proteins
Chemicals
Adaptor Proteins, Signal Transducing DNA-Binding Proteins Nuclear Proteins Phosphoproteins TEA Domain Transcription Factors TEAD1 protein, human Trans-Activators Transcription Factors YAP-Signaling Proteins YAP1 protein, human
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Li Ze
School of Life Sciences, Fudan University, Shanghai 200433, China.
Zhao Bin
Wang Ping
Chen Fei
Dong Zhenghong
Yang Huirong
Guan Kun-Liang
Xu Yanhui
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
1549-5477
DOI
10.1101/gad.1865810
Published
2010-02-01
Pages
235-40
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC2811825
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.1865810 PMC Full Text View journal details
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