6WXI

Colicin E1 fragment in nanodisc-embedded TolC

6WXI の概要

• エントリーDOI: 10.2210/pdb6wxi/pdb
• 関連するPDBエントリー: 6WXH
• EMDBエントリー: 21959 21960
• 分子名称: Outer membrane protein TolC (1 entity in total)
• 機能のキーワード: antibiotic efflux, bacteriocin, transport protein
• 由来する生物種: Escherichia coli (strain K12)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 161350.07

構造登録者

Kaelber, J.T.,Budiardjo, S.J.,Firlar, E.,Ikujuni, A.P.,Slusky, J.S.G. (登録日: 2020-05-10, 公開日: 2021-05-12, 最終更新日: 2024-05-15)

主引用文献

Budiardjo, S.J.,Stevens, J.J.,Calkins, A.L.,Ikujuni, A.P.,Wimalasena, V.K.,Firlar, E.,Case, D.A.,Biteen, J.S.,Kaelber, J.T.,Slusky, J.S.G.
Colicin E1 opens its hinge to plug TolC.
Elife, 11:-, 2022

PubMed Abstract: The double membrane architecture of Gram-negative bacteria forms a barrier that is impermeable to most extracellular threats. Bacteriocin proteins evolved to exploit the accessible, surface-exposed proteins embedded in the outer membrane to deliver cytotoxic cargo. Colicin E1 is a bacteriocin produced by, and lethal to, that hijacks the outer membrane proteins (OMPs) TolC and BtuB to enter the cell. Here, we capture the colicin E1 translocation domain inside its membrane receptor, TolC, by high-resolution cryo-electron microscopy to obtain the first reported structure of a bacteriocin bound to TolC. Colicin E1 binds stably to TolC as an open hinge through the TolC pore-an architectural rearrangement from colicin E1's unbound conformation. This binding is stable in live cells as indicated by single-molecule fluorescence microscopy. Finally, colicin E1 fragments binding to TolC plug the channel, inhibiting its native efflux function as an antibiotic efflux pump, and heightening susceptibility to three antibiotic classes. In addition to demonstrating that these protein fragments are useful starting points for developing novel antibiotic potentiators, this method could be expanded to other colicins to inhibit other OMP functions.

PubMed: 35199644
DOI: 10.7554/eLife.73297

実験手法

ELECTRON MICROSCOPY (2.84 Å)