Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, 80045, USA.
Department of Structural Biology, Stanford University, Stanford, CA, 94305, USA.
Nat Commun. 2022 Jun 8;13(1):3177. doi: 10.1038/s41467-022-30937-w.
The assembly and function of the yeast general transcription factor TFIID complex requires specific contacts between its Taf14 and Taf2 subunits, however, the mechanism underlying these contacts remains unclear. Here, we determined the molecular and structural basis by which the YEATS and ET domains of Taf14 bind to the C-terminal tail of Taf2 and identified a unique DNA-binding activity of the linker region connecting the two domains. We show that in the absence of ligands the linker region of Taf14 is occluded by the surrounding domains, and therefore the DNA binding function of Taf14 is autoinhibited. Binding of Taf2 promotes a conformational rearrangement in Taf14, resulting in a release of the linker for the engagement with DNA and the nucleosome. Genetic in vivo data indicate that the association of Taf14 with both Taf2 and DNA is essential for transcriptional regulation. Our findings provide a basis for deciphering the role of individual TFIID subunits in mediating gene transcription.
酵母一般转录因子 TFIID 复合物的组装和功能需要其 Taf14 和 Taf2 亚基之间的特定接触，但这些接触的机制仍不清楚。在这里，我们确定了 YEATS 和 ET 结构域的 Taf14 与 Taf2 羧基末端尾巴结合的分子和结构基础，并鉴定了连接两个结构域的连接区具有独特的 DNA 结合活性。我们表明，在没有配体的情况下，Taf14 的连接区被周围结构域封闭，因此 Taf14 的 DNA 结合功能被自动抑制。Taf2 的结合促进了 Taf14 的构象重排，导致连接区释放，与 DNA 和核小体结合。体内遗传数据表明，Taf14 与 Taf2 和 DNA 的结合对于转录调控是必不可少的。我们的发现为破译 TFIID 亚基在介导基因转录中的作用提供了基础。
