The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
Nat Commun. 2017 Jul 13;8:16072. doi: 10.1038/ncomms16072.
The mycobacteria RNA polymerase (RNAP) is a target for antimicrobials against tuberculosis, motivating structure/function studies. Here we report a 3.2 Å-resolution crystal structure of a Mycobacterium smegmatis (Msm) open promoter complex (RPo), along with structural analysis of the Msm RPo and a previously reported 2.76 Å-resolution crystal structure of an Msm transcription initiation complex with a promoter DNA fragment. We observe the interaction of the Msm RNAP α-subunit C-terminal domain (αCTD) with DNA, and we provide evidence that the αCTD may play a role in Mtb transcription regulation. Our results reveal the structure of an Actinobacteria-unique insert of the RNAP β' subunit. Finally, our analysis reveals the disposition of the N-terminal segment of Msm σ, which may comprise an intrinsically disordered protein domain unique to mycobacteria. The clade-specific features of the mycobacteria RNAP provide clues to the profound instability of mycobacteria RPo compared with E. coli.
分枝杆菌 RNA 聚合酶（RNAP）是抗结核药物的靶标，这激发了对其结构/功能的研究。在这里，我们报告了一个 3.2 Å 分辨率的分枝杆菌耻垢亚种（Msm）开放启动子复合物（RPo）的晶体结构，以及对 Msm RPo 和之前报道的 2.76 Å 分辨率的含有启动子 DNA 片段的 Msm 转录起始复合物的结构分析。我们观察到了 Msm RNAP α-亚基 C 末端结构域（αCTD）与 DNA 的相互作用，并提供了证据表明 αCTD 可能在 Mtb 转录调控中发挥作用。我们的结果揭示了 RNAP β'亚基的一个独特插入片段的结构。最后，我们的分析揭示了 Msm σ的 N 端片段的位置，它可能包含一个独特的、固有无序的蛋白结构域，仅存在于分枝杆菌中。分枝杆菌 RNAP 的分支特异性特征为分枝杆菌 RPo 与大肠杆菌相比的不稳定性提供了线索。
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