Bleichenbacher Michael, Tan Song, Richmond Timothy J
ETH Zürich, Institute for Molecular Biology and Biophysics, ETH-Hönggerberg, CH-8093 Zürich, Switzerland.
J Mol Biol. 2003 Sep 26;332(4):783-93. doi: 10.1016/s0022-2836(03)00887-8.
RNA polymerase II-dependent transcription requires the assembly of a multi-protein, preinitiation complex on core promoter elements. Transcription factor IID (TFIID) comprising the TATA box-binding protein (TBP) and TBP-associated factors (TAFs) is responsible for promoter recognition in this complex. Subsequent association of TFIIA and TFIIB provides enhanced complex stability. TFIIA is required for transcriptional stimulation by certain viral and cellular activators, and favors formation of the preinitiation complex in the presence of repressor NC2. The X-ray structures of human and yeast TBP/TFIIA/DNA complexes at 2.1A and 1.9A resolution, respectively, are presented here and seen to resemble each other closely. The interactions made by human TFIIA with TBP and DNA within and upstream of the TATA box, including those involving water molecules, are described and compared to the yeast structure. Of particular interest is a previously unobserved region of TFIIA that extends the binding interface with TBP in the yeast, but not in the human complex, and that further elucidates biochemical and genetic results.
RNA聚合酶II依赖性转录需要在核心启动子元件上组装多蛋白预起始复合物。由TATA盒结合蛋白（TBP）和TBP相关因子（TAFs）组成的转录因子IID（TFIID）负责该复合物中的启动子识别。随后TFIIA和TFIIB的结合增强了复合物的稳定性。TFIIA是某些病毒和细胞激活剂进行转录刺激所必需的，并且在存在阻遏物NC2的情况下有利于预起始复合物的形成。本文分别给出了分辨率为2.1埃和1.9埃的人类和酵母TBP/TFIIA/DNA复合物的X射线结构，发现它们彼此非常相似。描述了人类TFIIA与TATA盒内及其上游的TBP和DNA之间的相互作用，包括那些涉及水分子的相互作用，并与酵母结构进行了比较。特别有趣的是TFIIA的一个以前未观察到的区域，它在酵母中扩展了与TBP的结合界面，但在人类复合物中没有，并且进一步阐明了生化和遗传结果。
