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  3. Cryo-EM structures of lipopolysaccharide transporter LptB2FGC in lipopolysaccharide or AMP-PNP-bound states reveal its transport mechanism

Cryo-EM structures of lipopolysaccharide transporter LptB2FGC in lipopolysaccharide or AMP-PNP-bound states reveal its transport mechanism

  • Nat Commun. 2019 Sep 13;10(1):4175. doi: 10.1038/s41467-019-11977-1.
Xiaodi Tang 1,  Shenghai Chang 2 3,  Qinghua Luo 1,  Zhengyu Zhang 4,  Wen Qiao 1,  Caihuang Xu 2,  Changbin Zhang 1,  Yang Niu 1,  Wenxian Yang 1 5,  Ting Wang 1,  Zhibo Zhang 1,  Xiaofeng Zhu 1 5,  Xiawei Wei 1,  Changjiang Dong 6,  Xing Zhang 7 8,  Haohao Dong 9
Affiliations

Affiliations

  • 1 State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, 610041, Chengdu, China.
  • 2 Department of Pathology of Sir Run Run Shaw Hospital, and Department of Biophysics, Zhejiang University School of Medicine, 310058, Hangzhou, Zhejiang, China.
  • 3 Center of Cryo Electron Microscopy, Zhejiang University, 310058, Hangzhou, Zhejiang, China.
  • 4 Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, School of Pharmaceutical Sciences, Wuhan University, 430071, Wuhan, China.
  • 5 College of Life Science, Sichuan University, 610041, Chengdu, China.
  • 6 Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK. C.dong@uea.ac.uk.
  • 7 Department of Pathology of Sir Run Run Shaw Hospital, and Department of Biophysics, Zhejiang University School of Medicine, 310058, Hangzhou, Zhejiang, China. Xzhang1999@zju.edu.cn.
  • 8 Center of Cryo Electron Microscopy, Zhejiang University, 310058, Hangzhou, Zhejiang, China. Xzhang1999@zju.edu.cn.
  • 9 State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, 610041, Chengdu, China. Haohaodong@scu.edu.cn.
PMID: 31519889 DOI: 10.1038/s41467-019-11977-1
Abstract

Lipopolysaccharides (LPS) of Gram-negative bacteria are critical for the defence against cytotoxic substances and must be transported from the inner membrane (IM) to the outer membrane (OM) through a bridge formed by seven membrane proteins (LptBFGCADE). The IM component LptB2FG powers the process through a yet unclarified mechanism. Here we report three high-resolution cryo-EM structures of LptB2FG alone and complexed with LptC (LptB2FGC), trapped in either the LPS- or AMP-PNP-bound state. The structures reveal conformational changes between these states and substrate binding with or without LptC. We identify two functional transmembrane arginine-containing loops interacting with the bound AMP-PNP and elucidate allosteric communications between the domains. AMP-PNP binding induces an inward rotation and shift of the transmembrane helices of LptFG and LptC to tighten the cavity, with the closure of two lateral gates, to eventually expel LPS into the bridge. Functional assays reveal the functionality of the LptF and LptG periplasmic domains. Our findings shed LIGHT on the LPS transport mechanism.

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