当前位置: X-MOL 学术Nat. Commun. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Toxin import through the antibiotic efflux channel TolC
Nature Communications ( IF 16.6 ) Pub Date : 2021-07-30 , DOI: 10.1038/s41467-021-24930-y
Nicholas G Housden 1 , Melissa N Webby 1 , Edward D Lowe 1 , Tarick J El-Baba 2 , Renata Kaminska 1 , Christina Redfield 1 , Carol V Robinson 2 , Colin Kleanthous 1
Affiliation  

Bacteria often secrete diffusible protein toxins (bacteriocins) to kill bystander cells during interbacterial competition. Here, we use biochemical, biophysical and structural analyses to show how a bacteriocin exploits TolC, a major outer-membrane antibiotic efflux channel in Gram-negative bacteria, to transport itself across the outer membrane of target cells. Klebicin C (KlebC), a rRNase toxin produced by Klebsiella pneumoniae, binds TolC of a related species (K. quasipneumoniae) with high affinity through an N-terminal, elongated helical hairpin domain common amongst bacteriocins. The KlebC helical hairpin opens like a switchblade to bind TolC. A cryo-EM structure of this partially translocated state, at 3.1 Å resolution, reveals that KlebC associates along the length of the TolC channel. Thereafter, the unstructured N-terminus of KlebC protrudes beyond the TolC iris, presenting a TonB-box sequence to the periplasm. Association with proton-motive force-linked TonB in the inner membrane drives toxin import through the channel. Finally, we demonstrate that KlebC binding to TolC blocks drug efflux from bacteria. Our results indicate that TolC, in addition to its known role in antibiotic export, can function as a protein import channel for bacteriocins.



中文翻译:

通过抗生素外排通道 TolC 输入毒素

在细菌间竞争过程中,细菌通常会分泌可扩散的蛋白质毒素(细菌素)来杀死旁观者细胞。在这里,我们使用生化、生物物理和结构分析来展示细菌素如何利用 TolC(革兰氏阴性细菌中的主要外膜抗生素外排通道)将自身运输穿过靶细胞的外膜。Klebicin C (KlebC),一种由肺炎克雷伯菌产生的 rRNase 毒素,结合相关物种(K. quasipneumoniae)的 TolC) 通过细菌素中常见的 N 端、细长的螺旋发夹结构域具有高亲和力。KlebC 螺旋发夹像弹簧刀一样打开以绑定 TolC。这种部分易位状态的冷冻电镜结构,分辨率为 3.1 Å,表明 KlebC 沿着 TolC 通道的长度结合。此后,KlebC 的非结构化 N 端突出到 TolC 虹膜之外,向周质呈现 TonB-box 序列。与内膜中与质子动力相关的 TonB 的关联驱动毒素通过通道输入。最后,我们证明 KlebC 与 TolC 的结合阻止了细菌的药物流出。我们的结果表明,除了已知的抗生素输出作用外,TolC 还可以作为细菌素的蛋白质输入通道。

更新日期:2021-07-30
down
wechat
bug