Structural basis for bacterial lipoprotein relocation by the transporter LolCDE

Xiaodi Tang, Shenghai Chang, Ke Zhang, Qinghua Luo, Zhengyu Zhang, Ting Wang, Wen Qiao, Chen Wang, Chongrong Shen, Zhibo Zhang, Xiaofeng Zhu, Xiawei Wei, Changjiang Dong, Xing Zhang, Haohao Dong

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Lipoproteins in the outer membrane of Gram-negative bacteria are involved in various vital physiological activities, including multidrug resistance. Synthesized in the cytoplasm and matured in the inner membrane, lipoproteins must be transported to the outer membrane through the Lol pathway mediated by the ATP-binding cassette transporter LolCDE in the inner membrane via an unknown mechanism. Here, we report cryo-EM structures of Escherichia coli LolCDE in apo, lipoprotein-bound, LolA-bound, ADP-bound and AMP-PNP-bound states at a resolution of 3.2–3.8 Å, covering the complete lipoprotein transport cycle. Mutagenesis and in vivo viability assays verify features of the structures and reveal functional residues and structural characteristics of LolCDE. The results provide insights into the mechanisms of sorting and transport of outer-membrane lipoproteins and may guide the development of novel therapies against multidrug-resistant Gram-negative bacteria.

Original languageEnglish
Pages (from-to)347-355
Number of pages9
JournalNature Structural & Molecular Biology
Volume28
Issue number4
Early online date29 Mar 2021
DOIs
Publication statusPublished - 1 Apr 2021

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