IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-26433-2.html
   My bibliography  Save this article

The hereditary mutation G51D unlocks a distinct fibril strain transmissible to wild-type α-synuclein

Author

Listed:
  • Yunpeng Sun

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

  • Houfang Long

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

  • Wencheng Xia

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

  • Kun Wang

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

  • Xia Zhang

    (ShanghaiTech University)

  • Bo Sun

    (ShanghaiTech University)

  • Qin Cao

    (Shanghai Jiao Tong University)

  • Yaoyang Zhang

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

  • Bin Dai

    (Shanghai Jiao Tong University)

  • Dan Li

    (Shanghai Jiao Tong University)

  • Cong Liu

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

Abstract

α-Synuclein (α-Syn) can form different fibril strains with distinct polymorphs and neuropathologies, which is associated with the clinicopathological variability in synucleinopathies. How different α-syn fibril strains are produced and selected under disease conditions remains poorly understood. In this study, we show that the hereditary mutation G51D induces α-syn to form a distinct fibril strain in vitro. The cryogenic electron microscopy (cryo-EM) structure of the G51D fibril strain was determined at 2.96 Å resolution. The G51D fibril displays a relatively small and extended serpentine fold distinct from other α-syn fibril structures. Moreover, we show by cryo-EM that wild-type (WT) α-syn can assembly into the G51D fibril strain via cross-seeding with G51D fibrils. Our study reveals a distinct structure of G51D fibril strain triggered by G51D mutation but feasibly adopted by both WT and G51D α-syn, which suggests the cross-seeding and strain selection of WT and mutant α-syn in familial Parkinson’s disease (fPD).

Suggested Citation

  • Yunpeng Sun & Houfang Long & Wencheng Xia & Kun Wang & Xia Zhang & Bo Sun & Qin Cao & Yaoyang Zhang & Bin Dai & Dan Li & Cong Liu, 2021. "The hereditary mutation G51D unlocks a distinct fibril strain transmissible to wild-type α-synuclein," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26433-2
    DOI: 10.1038/s41467-021-26433-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-26433-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-26433-2?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
    ---><---

    Citations

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


    Cited by:

    1. Dhruva D. Dhavale & Alexander M. Barclay & Collin G. Borcik & Katherine Basore & Deborah A. Berthold & Isabelle R. Gordon & Jialu Liu & Moses H. Milchberg & Jennifer Y. O’Shea & Michael J. Rau & Zacha, 2024. "Structure of alpha-synuclein fibrils derived from human Lewy body dementia tissue," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Youqi Tao & Yunpeng Sun & Shiran Lv & Wencheng Xia & Kun Zhao & Qianhui Xu & Qinyue Zhao & Lin He & Weidong Le & Yong Wang & Cong Liu & Dan Li, 2022. "Heparin induces α-synuclein to form new fibril polymorphs with attenuated neuropathology," Nature Communications, Nature, vol. 13(1), pages 1-9, 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_s41467-021-26433-2. 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.