IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v562y2018i7726d10.1038_s41586-018-0568-2.html
   My bibliography  Save this article

Crystal structure of a membrane-bound O-acyltransferase

Author

Listed:
  • Dan Ma

    (University of Washington)

  • Zhizhi Wang

    (University of Washington)

  • Christopher N. Merrikh

    (University of Washington)

  • Kevin S. Lang

    (University of Washington)

  • Peilong Lu

    (University of Washington)

  • Xin Li

    (University of Washington
    Nankai University)

  • Houra Merrikh

    (University of Washington
    University of Washington)

  • Zihe Rao

    (Nankai University
    CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
    ShanghaiTech University
    University of Chinese Academy of Sciences)

  • Wenqing Xu

    (University of Washington
    CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences)

Abstract

Membrane-bound O-acyltransferases (MBOATs) are a superfamily of integral transmembrane enzymes that are found in all kingdoms of life1. In bacteria, MBOATs modify protective cell-surface polymers. In vertebrates, some MBOAT enzymes—such as acyl-coenzyme A:cholesterol acyltransferase and diacylglycerol acyltransferase 1—are responsible for lipid biosynthesis or phospholipid remodelling2,3. Other MBOATs, including porcupine, hedgehog acyltransferase and ghrelin acyltransferase, catalyse essential lipid modifications of secreted proteins such as Wnt, hedgehog and ghrelin, respectively4–10. Although many MBOAT proteins are important drug targets, little is known about their molecular architecture and functional mechanisms. Here we present crystal structures of DltB, an MBOAT responsible for the d-alanylation of cell-wall teichoic acid in Gram-positive bacteria11–16, both alone and in complex with the d-alanyl donor protein DltC. DltB contains a ring of 11 peripheral transmembrane helices, which shield a highly conserved extracellular structural funnel extending into the middle of the lipid bilayer. The conserved catalytic histidine residue is located at the bottom of this funnel and is connected to the intracellular DltC through a narrow tunnel. Mutation of either the catalytic histidine or the DltC-binding site of DltB abolishes the d-alanylation of lipoteichoic acid and sensitizes the Gram-positive bacterium Bacillus subtilis to cell-wall stress, which suggests cross-membrane catalysis involving the tunnel. Structure-guided sequence comparison among DltB and vertebrate MBOATs reveals a conserved structural core and suggests that MBOATs from different organisms have similar catalytic mechanisms. Our structures provide a template for understanding structure–function relationships in MBOATs and for developing therapeutic MBOAT inhibitors.

Suggested Citation

  • Dan Ma & Zhizhi Wang & Christopher N. Merrikh & Kevin S. Lang & Peilong Lu & Xin Li & Houra Merrikh & Zihe Rao & Wenqing Xu, 2018. "Crystal structure of a membrane-bound O-acyltransferase," Nature, Nature, vol. 562(7726), pages 286-290, October.
  • Handle: RePEc:nat:nature:v:562:y:2018:i:7726:d:10.1038_s41586-018-0568-2
    DOI: 10.1038/s41586-018-0568-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-018-0568-2
    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/s41586-018-0568-2?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. Qing Zhang & Deqiang Yao & Bing Rao & Liyan Jian & Yang Chen & Kexin Hu & Ying Xia & Shaobai Li & Yafeng Shen & An Qin & Jie Zhao & Lu Zhou & Ming Lei & Xian-Cheng Jiang & Yu Cao, 2021. "The structural basis for the phospholipid remodeling by lysophosphatidylcholine acyltransferase 3," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    2. Pingfeng Zhang & Zheng Liu, 2024. "Structural insights into the transporting and catalyzing mechanism of DltB in LTA D-alanylation," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    3. Kun Wang & Chia-Wei Lee & Xuewu Sui & Siyoung Kim & Shuhui Wang & Aidan B. Higgs & Aaron J. Baublis & Gregory A. Voth & Maofu Liao & Tobias C. Walther & Robert V. Farese, 2023. "The structure of phosphatidylinositol remodeling MBOAT7 reveals its catalytic mechanism and enables inhibitor identification," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

    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:562:y:2018:i:7726:d:10.1038_s41586-018-0568-2. 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.