Department of Biophysics, and Department of Infectious Disease of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Gastroenterology and Hepatology, Minhang Hospital, Fudan University, Shanghai, China.
Nat Commun. 2024 Jun 6;15(1):4850. doi: 10.1038/s41467-024-49229-6.
Bacterial RNAP needs to form holoenzyme with σ factors to initiate transcription. While Staphylococcus aureus σ controls housekeeping functions, S. aureus σ regulates virulence, biofilm formation, persistence, cell internalization, membrane transport, and antimicrobial resistance. Besides the sequence difference, the spacers between the -35 element and -10 element of σ regulated promoters are shorter than those of σ regulated promoters. Therefore, how σ recognizes and initiates transcription from target promoters can not be inferred from that of the well studied σ. Here, we report the cryo-EM structures of S. aureus RNAP-promoter open complexes comprising σ and σ, respectively. Structural analyses, in combination with biochemical experiments, reveal the structural basis for the promoter specificity of S. aureus transcription. Although the -10 element of σ regulated promoters is recognized by domain σ as single-stranded DNA, the -10 element of σ regulated promoters is co-recognized by domains σ and σ as double-stranded DNA, accounting for the short spacers of σ regulated promoters. S. aureus RNAP is a validated target of antibiotics, and our structures pave the way for rational drug design targeting S. aureus RNAP.
细菌 RNA 聚合酶需要与 σ 因子形成全酶才能起始转录。金黄色葡萄球菌 σ 控制着管家功能，而金黄色葡萄球菌 σ 则调节着毒力、生物膜形成、持久性、细胞内化、膜转运和抗微生物耐药性。除了序列差异之外，σ 调控启动子的-35 元件和-10 元件之间的间隔比 σ 调控启动子的间隔短。因此，σ 如何识别和从靶启动子起始转录，不能从研究充分的 σ 推断出来。在这里，我们报道了金黄色葡萄球菌 RNA 聚合酶-启动子开放复合物的低温电镜结构，分别包含 σ 和 σ。结构分析结合生化实验揭示了金黄色葡萄球菌转录的启动子特异性的结构基础。尽管 σ 调控启动子的-10 元件被 σ 结构域识别为单链 DNA，但 σ 调控启动子的-10 元件被 σ 和 σ 结构域共同识别为双链 DNA，这解释了 σ 调控启动子的短间隔。金黄色葡萄球菌 RNA 聚合酶是抗生素的有效靶点，我们的结构为针对金黄色葡萄球菌 RNA 聚合酶的合理药物设计铺平了道路。
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