Molecular and Cell Biology Department and QB3 Institute, UC Berkeley, CA, USA; Howard Hughes Medical Institute, UC Berkeley, CA, USA; Molecular Biophysics and Integrative Bio-Imaging Division, Lawrence Berkeley National Lab, CA, USA.
Biophysics Graduate Group, UC Berkeley, CA, USA.
Curr Opin Struct Biol. 2017 Dec;47:60-66. doi: 10.1016/j.sbi.2017.05.015. Epub 2017 Jun 15.
TFIID is a critical component of the eukaryotic transcription pre-initiation complex (PIC) required for the recruitment of RNA Pol II to the start site of protein-coding genes. Within the PIC, TFIID's role is to recognize and bind core promoter sequences and recruit the rest of the PIC components. Due to its size and its conformational complexity, TFIID poses a serious challenge for structural characterization. The small amounts of purified TFIID that can be obtained by present methods of purification from endogenous sources has limited structural studies to cryo-EM visualization, which requires very small amounts of sample. Previous cryo-EM studies have shed light on how the extreme conformational flexibility of TFIID is involved in core promoter DNA binding. Recent progress in cryo-EM methodology has facilitated a parallel progress in the study of human TFIID, leading to an improvement in resolution and the identification of the structural elements in the complex directly involved in DNA interaction. While many questions remain unanswered, the present structural knowledge of human TFIID suggests a mechanism for the sequential engagement with different core promoter sequences and how it could be influenced by regulatory factors.
TFIID 是真核转录起始前复合物 (PIC) 的关键组成部分，对于 RNA Pol II 招募到蛋白编码基因的起始位点是必需的。在 PIC 中，TFIID 的作用是识别和结合核心启动子序列，并招募 PIC 的其余组件。由于其大小和构象复杂性，TFIID 的结构特征描述极具挑战性。目前从内源性来源通过纯化方法获得的少量纯化 TFIID 限制了结构研究仅限于 cryo-EM 可视化，而 cryo-EM 可视化需要非常少量的样品。先前的 cryo-EM 研究揭示了 TFIID 的极端构象灵活性如何参与核心启动子 DNA 结合。cryo-EM 方法学的最新进展促进了人类 TFIID 研究的平行进展，提高了分辨率，并确定了复合物中直接参与 DNA 相互作用的结构元素。虽然仍有许多问题尚未得到解答，但目前对人类 TFIID 的结构知识表明了其与不同核心启动子序列的顺序结合的机制，以及它如何受到调节因子的影响。
