7NG9

Trimeric efflux pump Klebsiella TolC

7NG9 の概要

• エントリーDOI: 10.2210/pdb7ng9/pdb
• EMDBエントリー: 12310
• 分子名称: Outer membrane channel protein (1 entity in total)
• 機能のキーワード: efflux pump, trimer, membrane protein
• 由来する生物種: Klebsiella quasipneumoniae
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 162176.03

構造登録者

Webby, M.N.,Housden, N.G.,Kleanthous, C. (登録日: 2021-02-08, 公開日: 2021-06-30, 最終更新日: 2024-07-10)

主引用文献

Housden, N.G.,Webby, M.N.,Lowe, E.D.,El-Baba, T.J.,Kaminska, R.,Redfield, C.,Robinson, C.V.,Kleanthous, C.
Toxin import through the antibiotic efflux channel TolC.
Nat Commun, 12:4625-4625, 2021

PubMed Abstract: 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.

PubMed: 34330923
DOI: 10.1038/s41467-021-24930-y

実験手法

ELECTRON MICROSCOPY (3.3 Å)