The Hippo signaling pathway, which plays a central role in the control of organ size in animals, is well conserved in metazoans. The most downstream elements of this pathway are the TEAD transcription factors that are regulated by their association with the transcriptional coactivator YAP. Therefore, the creation of the binding interface that ensures the formation of the YAP:TEAD complex is a critical molecular recognition event essential for the development/survival of many living organisms. In this report, using the available structural information on the YAP:TEAD complex, we study the TEAD‐binding domain of YAP from different animal species. This analysis of more than 400 amino acid sequences reveals that the residues from YAP involved in the formation of the two main contact regions with TEAD are very well conserved. Therefore, the binding interface between YAP and TEAD, as found in humans, probably appeared at an early evolutionary stage in metazoans. We find that, in contrast to most other animal species, several Actinopterygii species possess YAP variants with a different TEAD‐binding domain. However, these variants bind to TEAD with a similar affinity. Our studies show that the protein identified as a YAP homolog in Caenorhabditis elegans does not contain the TEAD‐binding domain found in YAP of other metazoans. Finally, we do not identify in non‐metazoan species, amino acid sequences containing both a TEAD‐binding domain, as in metazoan YAP, and WW domain(s).

中文翻译：

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动物 YAP 蛋白 TEAD 结合域的研究

Hippo 信号通路在动物器官大小的控制中起着核心作用，在后生动物中得到了很好的保护。该途径的最下游元件是 TEAD 转录因子，它们通过与转录共激活因子 YAP 的结合来调节。因此，确保 YAP:TEAD 复合物形成的结合界面的创建是对许多生物体的发育/生存至关重要的关键分子识别事件。在本报告中，我们利用 YAP:TEAD 复合物的可用结构信息，研究了来自不同动物物种的 YAP 的 TEAD 结合域。对 400 多个氨基酸序列的分析表明，与 TEAD 形成两个主要接触区域的 YAP 残基非常保守。所以，在人类中发现的 YAP 和 TEAD 之间的结合界面可能出现在后生动物的早期进化阶段。我们发现，与大多数其他动物物种相比，一些 Actinopterygii 物种拥有具有不同 TEAD 结合域的 YAP 变体。然而，这些变体以相似的亲和力与 TEAD 结合。我们的研究表明，该蛋白质被鉴定为 YAP 同源物秀丽隐杆线虫不包含在其他后生动物的 YAP 中发现的 TEAD 结合域。最后，我们没有在非后生动物物种中鉴定出同时包含 TEAD 结合结构域（如后生动物 YAP）和 WW 结构域的氨基酸序列。