MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
Laboratory of Microbial Genetics and Gene Expression, Institute of Microbiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
J Bacteriol. 2019 Jan 28;201(4). doi: 10.1128/JB.00583-18. Print 2019 Feb 15.
Bacterial RNA polymerase (RNAP) is essential for gene expression and as such is a valid drug target. Hence, it is imperative to know its structure and dynamics. Here, we present two as-yet-unreported forms of RNAP: core and holoenzyme containing σ but no other factors. Each form was detected by cryo-electron microscopy in two major conformations. Comparisons of these structures with known structures of other RNAPs reveal a high degree of conformational flexibility of the mycobacterial enzyme and confirm that region 1.1 of σ is directed into the primary channel of RNAP. Taken together, we describe the conformational changes of unrestrained mycobacterial RNAP. We describe here three-dimensional structures of core and holoenzyme forms of mycobacterial RNA polymerase (RNAP) solved by cryo-electron microscopy. These structures fill the thus-far-empty spots in the gallery of the pivotal forms of mycobacterial RNAP and illuminate the extent of conformational dynamics of this enzyme. The presented findings may facilitate future designs of antimycobacterial drugs targeting RNAP.
细菌 RNA 聚合酶（RNAP）对于基因表达至关重要，因此是一个有效的药物靶标。因此，了解其结构和动态是至关重要的。在这里，我们展示了两种迄今为止尚未报道的 RNAP 形式：含有σ但不含其他因子的核心酶和全酶。每种形式都通过冷冻电子显微镜在两种主要构象中检测到。将这些结构与其他 RNAP 的已知结构进行比较，揭示了分枝杆菌酶的高度构象灵活性，并证实了σ的区域 1.1 被定向到 RNAP 的主要通道中。总之，我们描述了不受约束的分枝杆菌 RNAP 的构象变化。我们在这里描述了通过冷冻电子显微镜解决的分枝杆菌 RNA 聚合酶（RNAP）核心酶和全酶形式的三维结构。这些结构填补了分枝杆菌 RNAP 关键形式的空白，并阐明了该酶构象动力学的程度。所提出的发现可能有助于未来设计针对 RNAP 的抗分枝杆菌药物。
