Structural basis of copper-efflux-regulator-dependent transcription activation.

Structural basis of copper-efflux-regulator-dependent transcription activation.
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铜流出调节因子依赖性转录激活的结构基础

DOI:
10.1016/j.isci.2021.102449
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发表时间:
2021-05-21
期刊:
影响因子:
5.8
通讯作者:
Liu B
Liu B
中科院分区:
综合性期刊2区
文献类型:
--
作者:
Shi W;Zhang B;Jiang Y;Liu C;Zhou W;Chen M;Yang Y;Hu Y;Liu B

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铜外排调节因子(CueR)是汞抗性调节因子(MerR)家族中的一个代表性的金属调节因子,控制着细菌中铜稳态调节基因的表达。CueR和其他MerR家族调节因子的转录激活机制是弯曲启动子DNA的间隔区。在这里,我们报告完整的CueR依赖的转录激活复合物的冷冻EM结构。结构表明CueR二聚体弯曲19 bp启动子间隔区,重新排列-35和-10元件,以便被σ70-RNA聚合酶全酶识别,并揭示了CueR亚基的DNA结合结构域(DBD)与σ70非保守区(σNCR)之间的先前未报道的相互作用。功能研究表明,CueR-σNCR相互作用在CueR依赖的转录中起辅助作用,辅助CueR二聚体弯曲启动子DNA的激活机制。由于DBD在序列和结构上高度保守,因此这种转录激活机制通常可被MerR家族调节剂使用。CueR二聚体通过弯曲启动子DNA激活转录结构揭示了σNCR和CueR之间的相互作用σNCR/CueR相互作用在CueR依赖的转录中起辅助作用生物科学;生物化学;结构生物学
The copper efflux regulator (CueR), a representative member of mercury resistance regulator (MerR) family metalloregulators, controls expression of copper homeostasis-regulating genes in bacteria. The mechanism of transcription activation by CueR and other MerR family regulators is bending the spacer domain of promoter DNA. Here, we report the cryo-EM structures of the intact CueR-dependent transcription activation complexes. The structures show that CueR dimer bends the 19-bp promoter spacer to realign the −35 and −10 elements for recognition by σ70-RNA polymerase holoenzyme and reveal a previously unreported interaction between the DNA-binding domain (DBD) from one CueR subunit and the σ70 nonconserved region (σNCR). Functional studies have shown that the CueR-σNCR interaction plays an auxiliary role in CueR-dependent transcription, assisting the activation mechanism of bending promoter DNA by CueR dimer. Because DBDs are highly conserved in sequence and structure, this transcription-activating mechanism could be generally used by MerR family regulators. Cryo-EM structures of intact CueR-TAC complex without and with RNA synthesis CueR dimer activates transcription through bending promoter DNA The structures reveal the interactions between σNCR and CueR The σNCR/CueR interactions play an auxiliary role in CueR-dependent transcription Biological Sciences; Biochemistry; Structural Biology
DOI: 10.1038/nmeth.2727
发表时间: 2014-01
期刊: NATURE METHODS
影响因子: 48
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Kucukelbir, Alp;Sigworth, Fred J.;Tagare, Hemant D.
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影响因子: --
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发表时间: 2004-12-01
影响因子: 2.2
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DOI: 10.1074/jbc.ra118.002161
发表时间: 2018-05-11
影响因子: 4.8
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通讯作者: Murakami, Katsuhiko S.