Crystal structure of TAZ-TEAD complex reveals a distinct interaction mode from that of YAP-TEAD complex

Sci Rep. 2017 May 17;7(1):2035. doi: 10.1038/s41598-017-02219-9.

Abstract

The Hippo pathway is a tumor suppressor pathway that is implicated in the regulation of organ size. The pathway has three components: the upstream regulatory factors, the kinase core, and the downstream transcriptional machinery, which consists of YAP, TAZ (transcription co-activators) and TEAD (transcription factor). Formation of YAP/TAZ-TEAD complexes leads to the transcription of growth-promoting genes. Herein, we report the crystal structure of TAZ-TEAD4 complex, which reveals two binding modes. The first is similar to the published YAP-TEAD structure. The second is a unique binding mode, whereby two molecules of TAZ bind to and bridge two molecules of TEAD4. We validated the latter using cross-linking and multi-angle light scattering. Using siRNA, we showed that TAZ knockdown leads to a decrease in TEAD4 dimerization. Lastly, results from luciferase assays, using YAP/TAZ transfected or knockdown cells, give support to the non-redundancy of YAP/TAZ co-activators in regulating gene expression in the Hippo pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Binding Sites
  • Cell Cycle Proteins
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism
  • Mice
  • Models, Molecular*
  • Muscle Proteins / chemistry*
  • Muscle Proteins / metabolism
  • Phosphoproteins / chemistry*
  • Phosphoproteins / metabolism
  • Protein Binding
  • Protein Conformation*
  • Protein Interaction Domains and Motifs
  • Protein Multimerization
  • Recombinant Fusion Proteins
  • Structure-Activity Relationship
  • Transcription Factors / chemistry*
  • Transcription Factors / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Muscle Proteins
  • Phosphoproteins
  • Recombinant Fusion Proteins
  • Taz protein, mouse
  • Tead4 protein, mouse
  • Transcription Factors
  • Yap1 protein, mouse