IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-27244-1.html
   My bibliography  Save this article

The structural basis for the phospholipid remodeling by lysophosphatidylcholine acyltransferase 3

Author

Listed:
  • Qing Zhang

    (Chinese Academy of Sciences, University of Chinese Academy of Sciences)

  • Deqiang Yao

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

  • Bing Rao

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

  • Liyan Jian

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

  • Yang Chen

    (Shanghai Jiao Tong University School of Medicine)

  • Kexin Hu

    (Shanghai Jiao Tong University School of Medicine)

  • Ying Xia

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

  • Shaobai Li

    (Shanghai Jiao Tong University School of Medicine)

  • Yafeng Shen

    (Shanghai Jiao Tong University School of Medicine)

  • An Qin

    (Shanghai Jiao Tong University School of Medicine)

  • Jie Zhao

    (Shanghai Jiao Tong University School of Medicine)

  • Lu Zhou

    (Fudan University)

  • Ming Lei

    (Shanghai Jiao Tong University School of Medicine)

  • Xian-Cheng Jiang

    (State University of New York Downstate Health Sciences University)

  • Yu Cao

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

Abstract

As the major component of cell membranes, phosphatidylcholine (PC) is synthesized de novo in the Kennedy pathway and then undergoes extensive deacylation-reacylation remodeling via Lands’ cycle. The re-acylation is catalyzed by lysophosphatidylcholine acyltransferase (LPCAT) and among the four LPCAT members in human, the LPCAT3 preferentially introduces polyunsaturated acyl onto the sn-2 position of lysophosphatidylcholine, thereby modulating the membrane fluidity and membrane protein functions therein. Combining the x-ray crystallography and the cryo-electron microscopy, we determined the structures of LPCAT3 in apo-, acyl donor-bound, and acyl receptor-bound states. A reaction chamber was revealed in the LPCAT3 structure where the lysophosphatidylcholine and arachidonoyl-CoA were positioned in two tunnels connected near to the catalytic center. A side pocket was found expanding the tunnel for the arachidonoyl CoA and holding the main body of arachidonoyl. The structural and functional analysis provides the basis for the re-acylation of lysophosphatidylcholine and the substrate preference during the reactions.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27244-1
    DOI: 10.1038/s41467-021-27244-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-27244-1
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-021-27244-1?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
    ---><---

    References listed on IDEAS

    as
    1. Lie Wang & Hongwu Qian & Yin Nian & Yimo Han & Zhenning Ren & Hanzhi Zhang & Liya Hu & B. V. Venkataram Prasad & Arthur Laganowsky & Nieng Yan & Ming Zhou, 2020. "Structure and mechanism of human diacylglycerol O-acyltransferase 1," Nature, Nature, vol. 581(7808), pages 329-332, May.
    2. Xuewu Sui & Kun Wang & Nina L. Gluchowski & Shane D. Elliott & Maofu Liao & Tobias C. Walther & Robert V. Farese, 2020. "Structure and catalytic mechanism of a human triacylglycerol-synthesis enzyme," Nature, Nature, vol. 581(7808), pages 323-328, May.
    3. 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.
    4. Yufei Han & Qian Zhuang & Bo Sun & Wenping Lv & Sheng Wang & Qingjie Xiao & Bin Pang & Youli Zhou & Fuxing Wang & Pengliang Chi & Qisheng Wang & Zhen Li & Lizhe Zhu & Fuping Li & Dong Deng & Ying-Chih, 2021. "Crystal structure of steroid reductase SRD5A reveals conserved steroid reduction mechanism," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    5. Chengcheng Guan & Yange Niu & Si-Cong Chen & Yunlu Kang & Jing-Xiang Wu & Koji Nishi & Catherine C. Y. Chang & Ta-Yuan Chang & Tuoping Luo & Lei Chen, 2020. "Structural insights into the inhibition mechanism of human sterol O-acyltransferase 1 by a competitive inhibitor," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    Full references (including those not matched with items on IDEAS)

    Citations

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


    Cited by:

    1. 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.
    2. Xuewu Sui & Kun Wang & Kangkang Song & Chen Xu & Jiunn Song & Chia-Wei Lee & Maofu Liao & Robert V. Farese & Tobias C. Walther, 2023. "Mechanism of action for small-molecule inhibitors of triacylglycerol synthesis," Nature Communications, Nature, vol. 14(1), pages 1-10, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. 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.
    2. Xuewu Sui & Kun Wang & Kangkang Song & Chen Xu & Jiunn Song & Chia-Wei Lee & Maofu Liao & Robert V. Farese & Tobias C. Walther, 2023. "Mechanism of action for small-molecule inhibitors of triacylglycerol synthesis," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    3. 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.
    4. Geng Chen & Xiankun Wang & Qiwen Liao & Yunjun Ge & Haizhan Jiao & Qiang Chen & Yezhou Liu & Wenping Lyu & Lizhe Zhu & Gydo C. P. Zundert & Michael J. Robertson & Georgios Skiniotis & Yang Du & Hongli, 2022. "Structural basis for recognition of N-formyl peptides as pathogen-associated molecular patterns," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    5. 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.
    6. Yong Jiang & Zhong Zhuang & Wenqian Jia & Ming Xie & Zhengkui Zhou & Jing Tang & Hao Bai & Guobin Chang & Guohong Chen & Shuisheng Hou, 2022. "Comparative Transcriptome Analysis Reveals the Key Genes Involved in Lipid Deposition in Pekin Ducks ( Anas platyrhynchos domesticus )," Agriculture, MDPI, vol. 12(11), pages 1-19, October.
    7. Wenhao Cui & Yange Niu & Zejian Sun & Rui Liu & Lei Chen, 2023. "Structures of human SGLT in the occluded state reveal conformational changes during sugar transport," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    8. Iris D. Zelnik & Beatriz Mestre & Jonathan J. Weinstein & Tamir Dingjan & Stav Izrailov & Shifra Ben-Dor & Sarel J. Fleishman & Anthony H. Futerman, 2023. "Computational design and molecular dynamics simulations suggest the mode of substrate binding in ceramide synthases," Nature Communications, Nature, vol. 14(1), pages 1-6, December.
    9. Yange Niu & Wenhao Cui & Rui Liu & Sanshan Wang & Han Ke & Xiaoguang Lei & Lei Chen, 2022. "Structural mechanism of SGLT1 inhibitors," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    10. Dianne Lumaquin-Yin & Emily Montal & Eleanor Johns & Arianna Baggiolini & Ting-Hsiang Huang & Yilun Ma & Charlotte LaPlante & Shruthy Suresh & Lorenz Studer & Richard M. White, 2023. "Lipid droplets are a metabolic vulnerability in melanoma," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    11. Lie Wang & Ming Zhou, 2023. "Structure of a eukaryotic cholinephosphotransferase-1 reveals mechanisms of substrate recognition and catalysis," Nature Communications, Nature, vol. 14(1), pages 1-8, 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:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27244-1. 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.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with 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.