IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v549y2017i7671d10.1038_nature23649.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature23649
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/nature23649?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    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. 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.
    4. Sheng Shu & Wei Mi, 2022. "Regulatory mechanisms of lipopolysaccharide synthesis in Escherichia coli," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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.
    11. 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.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:549:y:2017:i:7671:d:10.1038_nature23649. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.