Roberts S G, Green M R
Howard Hughes Medical Institute, Program in Molecular Medicine, University of Massachusetts Medical Center, Worcester 01605.
Nature. 1994 Oct 20;371(6499):717-20. doi: 10.1038/371717a0.
Transcriptional activator proteins (activators) function, at least in part, by increasing preinitiation complex assembly (for reviews see refs 1-4). Previous studies have shown that an acidic activator forms a contact with the general transcription factor TFIIB (refs 5-7) and recruits it into the preinitiation complex. Mutational studies indicate that this interaction between the acidic activator and TFIIB is required for transcriptional stimulation. We show here that the acidic activator-TFIIB interaction has an additional function in preinitiation complex assembly. We provide evidence that in native TFIIB the amino- and carboxy-terminal domains are engaged in an intramolecular interaction. The acidic activator disrupts this intramolecular interaction to expose binding sites for general transcription factors that enter the preinitiation complex through association with TFIIB. Thus, the acidic activator induces a conformational change in TFIIB that drives preinitiation complex assembly forward.
转录激活蛋白（激活剂）的功能至少部分是通过增加起始前复合物的组装来实现的（综述见参考文献1 - 4）。先前的研究表明，酸性激活剂与通用转录因子TFIIB形成接触（参考文献5 - 7），并将其招募到起始前复合物中。突变研究表明，酸性激活剂与TFIIB之间的这种相互作用是转录激活所必需的。我们在此表明，酸性激活剂 - TFIIB相互作用在起始前复合物组装中具有额外功能。我们提供的证据表明，在天然TFIIB中，氨基末端和羧基末端结构域参与了分子内相互作用。酸性激活剂破坏这种分子内相互作用，以暴露通过与TFIIB结合进入起始前复合物的通用转录因子的结合位点。因此，酸性激活剂诱导TFIIB发生构象变化，从而推动起始前复合物的组装向前进行。
