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Structural basis of MsbA-mediated lipopolysaccharide transport

Author

Listed:
  • Wei Mi

    (Harvard Medical School)

  • Yanyan Li

    (State Key Laboratory of Food Science and Technology, Jiangnan University)

  • Sung Hwan Yoon

    (School of Dentistry, University of Maryland)

  • Robert K. Ernst

    (School of Dentistry, University of Maryland)

  • Thomas Walz

    (Laboratory of Molecular Electron Microscopy, The Rockefeller University)

  • Maofu Liao

    (Harvard Medical School)

Abstract

Lipopolysaccharide (LPS) in the outer membrane of Gram-negative bacteria is critical for the assembly of their cell envelopes. LPS synthesized in the cytoplasmic leaflet of the inner membrane is flipped to the periplasmic leaflet by MsbA, an ATP-binding cassette transporter. Despite substantial efforts, the structural mechanisms underlying MsbA-driven LPS flipping remain elusive. Here we use single-particle cryo-electron microscopy to elucidate the structures of lipid-nanodisc-embedded MsbA in three functional states. The 4.2 Å-resolution structure of the transmembrane domains of nucleotide-free MsbA reveals that LPS binds deep inside MsbA at the height of the periplasmic leaflet, establishing extensive hydrophilic and hydrophobic interactions with MsbA. Two sub-nanometre-resolution structures of MsbA with ADP-vanadate and ADP reveal an unprecedented closed and an inward-facing conformation, respectively. Our study uncovers the structural basis for LPS recognition, delineates the conformational transitions of MsbA to flip LPS, and paves the way for structural characterization of other lipid flippases.

Suggested Citation

  • Wei Mi & Yanyan Li & Sung Hwan Yoon & Robert K. Ernst & Thomas Walz & Maofu Liao, 2017. "Structural basis of MsbA-mediated lipopolysaccharide transport," Nature, Nature, vol. 549(7671), pages 233-237, September.
    • Handle: RePEc:nat:nature:v:549:y:2017:i:7671:d:10.1038_nature23649
    DOI: 10.1038/nature23649
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    Cited by:

    1. Tianqi Zhang & Jixing Lyu & Bowei Yang & Sangho D. Yun & Elena Scott & Minglei Zhao & Arthur Laganowsky, 2024. "Native mass spectrometry and structural studies reveal modulation of MsbA–nucleotide interactions by lipids," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    2. Lin Yu & Xin Xu & Wan-Zhen Chua & Hao Feng & Zheng Ser & Kai Shao & Jian Shi & Yumei Wang & Zongli Li & Radoslaw M. Sobota & Lok-To Sham & Min Luo, 2023. "Structural basis of peptide secretion for Quorum sensing by ComA," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. Sheng Cao & Yihu Yang & Lili He & Yumo Hang & Xiaodong Yan & Hui Shi & Jiaquan Wu & Zhuqing Ouyang, 2023. "Cryo-EM structures of mitochondrial ABC transporter ABCB10 in apo and biliverdin-bound form," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    4. Jere P. Segrest & Chongren Tang & Hyun D. Song & Martin K. Jones & W. Sean Davidson & Stephen G. Aller & Jay W. Heinecke, 2022. "ABCA1 is an extracellular phospholipid translocase," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    5. Shana Bergman & Rosemary J. Cater & Ambrose Plante & Filippo Mancia & George Khelashvili, 2023. "Substrate binding-induced conformational transitions in the omega-3 fatty acid transporter MFSD2A," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    6. Jixing Lyu & Chang Liu & Tianqi Zhang & Samantha Schrecke & Nicklaus P. Elam & Charles Packianathan & Georg K. A. Hochberg & David Russell & Minglei Zhao & Arthur Laganowsky, 2022. "Structural basis for lipid and copper regulation of the ABC transporter MsbA," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    7. Shuhui Wang & Kun Wang & Kangkang Song & Zon Weng Lai & Pengfei Li & Dongying Li & Yajie Sun & Ye Mei & Chen Xu & Maofu Liao, 2024. "Structures of the Mycobacterium tuberculosis efflux pump EfpA reveal the mechanisms of transport and inhibition," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    8. Qingyu Tang & Matt Sinclair & Hale S. Hasdemir & Richard A. Stein & Erkan Karakas & Emad Tajkhorshid & Hassane S. Mchaourab, 2023. "Asymmetric conformations and lipid interactions shape the ATP-coupled cycle of a heterodimeric ABC transporter," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    9. Sheng Shu & Wei Mi, 2022. "Regulatory mechanisms of lipopolysaccharide synthesis in Escherichia coli," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    10. Zhi-Peng Chen & Da Xu & Liang Wang & Yao-Xu Mao & Yang Li & Meng-Ting Cheng & Cong-Zhao Zhou & Wen-Tao Hou & Yuxing Chen, 2022. "Structural basis of substrate recognition and translocation by human very long-chain fatty acid transporter ABCD1," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    11. Elisabeth Lambert & Ahmad Reza Mehdipour & Alexander Schmidt & Gerhard Hummer & Camilo Perez, 2022. "Evidence for a trap-and-flip mechanism in a proton-dependent lipid transporter," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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