Structure of the RhlR-PqsE complex from Pseudomonas aeruginosa reveals mechanistic insights into quorum-sensing gene regulation.
Structure of the RhlR-PqsE complex from Pseudomonas aeruginosa reveals mechanistic insights into quorum-sensing gene regulation.
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DOI：
10.1016/j.str.2022.10.008
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发表时间：
2022-12-01
期刊：
影响因子：
5.7
通讯作者：
Paczkowski, Jon E.
中科院分区：
文献类型：
--
作者：
Feathers, J. Ryan;Richael, Erica K.;Simanek, Kayla A.;Fromme, J. Christopher;Paczkowski, Jon E.
铜绿假单胞菌是一种机会致病菌，每年在美国造成数千人死亡。铜绿假单胞菌毒力因子的产生是由群体感应介导的，群体感应是一种细菌细胞间通讯的机制，依赖于称为自诱导物的信号分子的产生和检测。在铜绿假单胞菌中，转录因子受体RhlR被RhII合成的自诱导物激活。我们最近表明，RhlR依赖的转录增强的物理相互作用与酶PqsE通过增加的亲和力RhlR的启动子DNA。然而，复合物形成的分子基础以及复合物形成如何增强RhlR转录活性仍不清楚。在这里，我们报告的配体结合RhlR的结构与PqsE复合。此外，我们确定了与DNA结合的复合物的结构，揭示了PqsE增强RhlR介导的转录的机制，从而建立了铜绿假单胞菌中RhlR依赖性毒力因子产生的分子基础。Feathers等人确定了与PqsE结合的群体感应受体RhlR的结构，PqsE是铜绿假单胞菌中致病所需的复合物。这些结构和伴随的数据建立了RhlR活化的基础，为未来的药物发现工作提供了模板，以破坏铜绿假单胞菌中的致病性信号传导。
Pseudomonas aeruginosa is an opportunistic pathogen that is responsible for thousands of deaths every year in the United States. P. aeruginosa virulence factor production is mediated by quorum sensing, a mechanism of bacterial cell-cell communication that relies on the production and detection of signal molecules called autoinducers. In P. aeruginosa, the transcription factor receptor RhlR is activated by a RhlI-synthesized autoinducer. We recently showed that RhlR-dependent transcription is enhanced by a physical interaction with the enzyme PqsE via increased affinity of RhlR for promoter DNA. However, the molecular basis for complex formation and how complex formation enhanced RhlR transcriptional activity remained unclear. Here, we report the structure of ligand-bound RhlR in complex with PqsE. Additionally, we determined the structure of the complex bound with DNA, revealing the mechanism by which RhlR mediated transcription is enhanced by PqsE, thereby establishing the molecular basis for RhlR-dependent virulence factor production in P. aeruginosa. Feathers et al. determined the structure of the quorum-sensing receptor RhlR bound to PqsE, a complex required for pathogenesis in Pseudomonas aeruginosa. The structures and accompanying data established the basis for RhlR activation, providing a template for future drug discovery efforts to disrupt pathogenic signaling in P. aeruginosa.
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影响因子：
3.2
作者：
BRINT, JM;OHMAN, DE
通讯作者：
OHMAN, DE
影响因子：
5.8
作者：
Glaser, F;Pupko, T;Ben-Tal, N
通讯作者：
Ben-Tal, N
DOI：
10.1107/s2059798318009324
发表时间：
2018-09-01
期刊：
Acta crystallographica. Section D, Structural biology
影响因子：
--
作者：
Afonine PV;Klaholz BP;Moriarty NW;Poon BK;Sobolev OV;Terwilliger TC;Adams PD;Urzhumtsev A
通讯作者：
Urzhumtsev A
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
4.8
作者：
Bottomley, Matthew J.;Muraglia, Ester;Carfi, Andrea
通讯作者：
Carfi, Andrea