IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-31240-4.html
   My bibliography  Save this article

Cryo-EM structure of an amyloid fibril formed by full-length human SOD1 reveals its conformational conversion

Author

Listed:
  • Li-Qiang Wang

    (Wuhan University
    Wuhan University Shenzhen Research Institute)

  • Yeyang Ma

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

  • Han-Ye Yuan

    (Wuhan University
    Wuhan University Shenzhen Research Institute)

  • Kun Zhao

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

  • Mu-Ya Zhang

    (Wuhan University
    Wuhan University Shenzhen Research Institute)

  • Qiang Wang

    (Huazhong Agricultural University)

  • Xi Huang

    (Jinan University (Shenzhen People’s Hospital))

  • Wen-Chang Xu

    (Wuhan University)

  • Bin Dai

    (Shanghai Jiao Tong University)

  • Jie Chen

    (Wuhan University
    Wuhan University Shenzhen Research Institute)

  • Dan Li

    (Shanghai Jiao Tong University
    Shanghai Jiao Tong University)

  • Delin Zhang

    (Huazhong Agricultural University)

  • Zhengzhi Wang

    (Wuhan University)

  • Liangyu Zou

    (Jinan University (Shenzhen People’s Hospital))

  • Ping Yin

    (Huazhong Agricultural University)

  • Cong Liu

    (Chinese Academy of Sciences)

  • Yi Liang

    (Wuhan University
    Wuhan University Shenzhen Research Institute)

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. Misfolded Cu, Zn-superoxide dismutase (SOD1) has been linked to both familial and sporadic ALS. SOD1 fibrils formed in vitro share toxic properties with ALS inclusions. Here we produced cytotoxic amyloid fibrils from full-length apo human SOD1 under reducing conditions and determined the atomic structure using cryo-EM. The SOD1 fibril consists of a single protofilament with a left-handed helix. The fibril core exhibits a serpentine fold comprising N-terminal segment (residues 3–55) and C-terminal segment (residues 86–153) with an intrinsic disordered segment. The two segments are zipped up by three salt bridge pairs. By comparison with the structure of apo SOD1 dimer, we propose that eight β-strands (to form a β-barrel) and one α-helix in the subunit of apo SOD1 convert into thirteen β-strands stabilized by five hydrophobic cavities in the SOD1 fibril. Our data provide insights into how SOD1 converts between structurally and functionally distinct states.

Suggested Citation

  • Li-Qiang Wang & Yeyang Ma & Han-Ye Yuan & Kun Zhao & Mu-Ya Zhang & Qiang Wang & Xi Huang & Wen-Chang Xu & Bin Dai & Jie Chen & Dan Li & Delin Zhang & Zhengzhi Wang & Liangyu Zou & Ping Yin & Cong Liu , 2022. "Cryo-EM structure of an amyloid fibril formed by full-length human SOD1 reveals its conformational conversion," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31240-4
    DOI: 10.1038/s41467-022-31240-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-31240-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-31240-4?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. Lynn Radamaker & Julian Baur & Stefanie Huhn & Christian Haupt & Ute Hegenbart & Stefan Schönland & Akanksha Bansal & Matthias Schmidt & Marcus Fändrich, 2021. "Cryo-EM reveals structural breaks in a patient-derived amyloid fibril from systemic AL amyloidosis," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    Full references (including those not matched with items on IDEAS)

    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. Sara Karimi-Farsijani & Peter Benedikt Pfeiffer & Sambhasan Banerjee & Julian Baur & Lukas Kuhn & Niklas Kupfer & Ute Hegenbart & Stefan O. Schönland & Sebastian Wiese & Christian Haupt & Matthias Sch, 2024. "Light chain mutations contribute to defining the fibril morphology in systemic AL amyloidosis," Nature Communications, Nature, vol. 15(1), pages 1-8, December.
    2. Binh An Nguyen & Virender Singh & Shumaila Afrin & Anna Yakubovska & Lanie Wang & Yasmin Ahmed & Rose Pedretti & Maria del Carmen Fernandez-Ramirez & Preeti Singh & Maja Pękała & Luis O. Cabrera Herna, 2024. "Structural polymorphism of amyloid fibrils in ATTR amyloidosis revealed by cryo-electron microscopy," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    3. Martin Wilkinson & Rodrigo U. Gallardo & Roberto Maya Martinez & Nicolas Guthertz & Masatomo So & Liam D. Aubrey & Sheena E. Radford & Neil A. Ranson, 2023. "Disease-relevant β2-microglobulin variants share a common amyloid fold," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    4. Kartikay Sharma & Fabian Stockert & Jayakrishna Shenoy & Mélanie Berbon & Muhammed Bilal Abdul-Shukkoor & Birgit Habenstein & Antoine Loquet & Matthias Schmidt & Marcus Fändrich, 2024. "Cryo-EM observation of the amyloid key structure of polymorphic TDP-43 amyloid fibrils," Nature Communications, Nature, vol. 15(1), pages 1-8, December.
    5. Tim Schulte & Antonio Chaves-Sanjuan & Valentina Speranzini & Kevin Sicking & Melissa Milazzo & Giulia Mazzini & Paola Rognoni & Serena Caminito & Paolo Milani & Chiara Marabelli & Alessandro Corbelli, 2024. "Helical superstructures between amyloid and collagen in cardiac fibrils from a patient with AL amyloidosis," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    6. Maximilian Steinebrei & Julian Baur & Anaviggha Pradhan & Niklas Kupfer & Sebastian Wiese & Ute Hegenbart & Stefan O. Schönland & Matthias Schmidt & Marcus Fändrich, 2023. "Common transthyretin-derived amyloid fibril structures in patients with hereditary ATTR amyloidosis," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    7. Maximilian Steinebrei & Juliane Gottwald & Julian Baur & Christoph Röcken & Ute Hegenbart & Stefan Schönland & Matthias Schmidt, 2022. "Cryo-EM structure of an ATTRwt amyloid fibril from systemic non-hereditary transthyretin amyloidosis," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    8. Tejaswini Pradhan & Riddhiman Sarkar & Kevin M. Meighen-Berger & Matthias J. Feige & Martin Zacharias & Bernd Reif, 2023. "Mechanistic insights into the aggregation pathway of the patient-derived immunoglobulin light chain variable domain protein FOR005," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    9. Lynn Radamaker & Sara Karimi-Farsijani & Giada Andreotti & Julian Baur & Matthias Neumann & Sarah Schreiner & Natalie Berghaus & Raoul Motika & Christian Haupt & Paul Walther & Volker Schmidt & Stefan, 2021. "Role of mutations and post-translational modifications in systemic AL amyloidosis studied by cryo-EM," Nature Communications, Nature, vol. 12(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:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31240-4. 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.