Kaan, H.Y.K., Chan, S.W., Tan, S.K.J. et al. Crystal structure of TAZ-TEAD complex reveals a distinct interaction mode from that of YAP-TEAD complex. Sci Rep 7, 2035 (2017). https://doi.org/10.1038/s41598-017-02219-9
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.
We thank Jean, Yuch-Cheng and other beamline scientists for their support at the NSRRC beamline BL13C1. We also thank Kit Yeung (Pär Nordlund’s lab) for her help in using and analyzing data for MALS. This work is financially supported by the Agency for Science, Technology, and Research (A*STAR), and NMRC Open Fund Individual Research (OF-IRG) Grant (No. NMRC/OFIRG/0024/2016) in Singapore.
This is a version of record published in Scientific Reports. The final authenticated version is available online at: https://doi.org/10.1038/s41598-017-02219-9