Structural insights into the YAP and TEAD complex
Structural insights into the YAP and TEAD complex
复制标题
YAP 和 TEAD 综合体的结构见解
DOI：
10.1101/gad.1865810
复制
发表时间：
2010-02-01
影响因子：
10.5
通讯作者：
Xu, Yanhui
中科院分区：
文献类型：
--
作者：
Li, Ze;Zhao, Bin;Xu, Yanhui
yes相关蛋白（YAP）转录辅激活因子是器官大小的关键调节因子，也是被Hippo肿瘤抑制通路抑制的候选人类癌基因。TEAD家族转录因子直接结合并介导yap诱导的基因表达。本文报道了YAP（残基50-171）-TEAD1（残基194-411）复合物的三维结构，其中YAP包裹在TEAD1的球状结构周围，并通过三个高度保守的界面形成广泛的相互作用。界面3，包括YAP残基86-100，对于复杂的形成最为关键。我们的研究揭示了YAP-TEAD相互作用的生化性质，为YAP-TEAD过度激活在人类疾病中的药理干预提供了依据。
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.