6SGU

Cryo-EM structure of Escherichia coli AcrB and DARPin in Saposin A-nanodisc

6SGU の概要

• エントリーDOI: 10.2210/pdb6sgu/pdb
• EMDBエントリー: 10185
• 分子名称: Multidrug efflux pump subunit AcrB, DARPin (2 entities in total)
• 機能のキーワード: rnd transporter, efflux pump, drug transport, antibiotic resistance, lipid nanodisc, membrane protein
• 由来する生物種: Escherichia coli K12; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 377630.67

構造登録者

Szewczak-Harris, A.,Du, D.,Newman, C.,Neuberger, A.,Luisi, B.F. (登録日: 2019-08-05, 公開日: 2020-05-13, 最終更新日: 2025-07-09)

主引用文献

Du, D.,Neuberger, A.,Orr, M.W.,Newman, C.E.,Hsu, P.C.,Samsudin, F.,Szewczak-Harris, A.,Ramos, L.M.,Debela, M.,Khalid, S.,Storz, G.,Luisi, B.F.
Interactions of a Bacterial RND Transporter with a Transmembrane Small Protein in a Lipid Environment.
Structure, 28:625-, 2020

PubMed Abstract: The small protein AcrZ in Escherichia coli interacts with the transmembrane portion of the multidrug efflux pump AcrB and increases resistance of the bacterium to a subset of the antibiotic substrates of that transporter. It is not clear how the physical association of the two proteins selectively changes activity of the pump for defined substrates. Here, we report cryo-EM structures of AcrB and the AcrBZ complex in lipid environments, and comparisons suggest that conformational changes occur in the drug-binding pocket as a result of AcrZ binding. Simulations indicate that cardiolipin preferentially interacts with the AcrBZ complex, due to increased contact surface, and we observe that chloramphenicol sensitivity of bacteria lacking AcrZ is exacerbated when combined with cardiolipin deficiency. Taken together, the data suggest that AcrZ and lipid cooperate to allosterically modulate AcrB activity. This mode of regulation by a small protein and lipid may occur for other membrane proteins.

PubMed: 32348749
DOI: 10.1016/j.str.2020.03.013

実験手法

ELECTRON MICROSCOPY (3.27 Å)