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-Structure paper
タイトル | Toxin import through the antibiotic efflux channel TolC. |
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ジャーナル・号・ページ | Nat Commun, Vol. 12, Issue 1, Page 4625, Year 2021 |
掲載日 | 2021年7月30日 |
著者 | Nicholas G Housden / Melissa N Webby / Edward D Lowe / Tarick J El-Baba / Renata Kaminska / Christina Redfield / Carol V Robinson / Colin Kleanthous / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Commun / PubMed:34330923 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 1.901 - 3.3 Å |
構造データ | EMDB-12309, PDB-7ng8: EMDB-12310, PDB-7ng9: PDB-7nna: |
化合物 | ChemComp-HOH: |
由来 |
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キーワード | MEMBRANE PROTEIN / Efflux pump / trimer / complex / ANTIBIOTIC / TOXIN / IMPORT |