IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-41838-x.html
   My bibliography  Save this article

Cryo-electron microscopy of IgM-VAR2CSA complex reveals IgM inhibits binding of Plasmodium falciparum to Chondroitin Sulfate A

Author

Listed:
  • Reetesh Raj Akhouri

    (Okinawa Institute of Science and Technology Graduate University
    Indian Institute of Technology Madras)

  • Suchi Goel

    (Indian Institute of Science Education and Research Tirupati)

  • Ulf Skoglund

    (Okinawa Institute of Science and Technology Graduate University)

Abstract

Placental malaria is caused by Plasmodium falciparum-infected erythrocytes (IEs) adhering to chondroitin sulfate proteoglycans in placenta via VAR2CSA-type PfEMP1. Human pentameric immunoglobulin M (IgM) binds to several types of PfEMP1, including VAR2CSA via its Fc domain. Here, a 3.6 Å cryo-electron microscopy map of the IgM-VAR2CSA complex reveals that two molecules of VAR2CSA bind to the Cµ4 of IgM through their DBL3X and DBL5ε domains. The clockwise and anti-clockwise rotation of the two VAR2CSA molecules on opposite faces of IgM juxtaposes C-termini of both VAR2CSA near the J chain, where IgM creates a wall between both VAR2CSA molecules and hinders its interaction with its receptor. To support this, we show when VAR2CSA is bound to IgM, its staining on IEs as well as binding of IEs to chondroitin sulfate A in vitro is severely compromised.

Suggested Citation

  • Reetesh Raj Akhouri & Suchi Goel & Ulf Skoglund, 2023. "Cryo-electron microscopy of IgM-VAR2CSA complex reveals IgM inhibits binding of Plasmodium falciparum to Chondroitin Sulfate A," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41838-x
    DOI: 10.1038/s41467-023-41838-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-41838-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-41838-x?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. Kaituo Wang & Robert Dagil & Thomas Lavstsen & Sandeep K. Misra & Charlotte B. Spliid & Yong Wang & Tobias Gustavsson & Daniel R. Sandoval & Elena Ethel Vidal-Calvo & Swati Choudhary & Mette Ø Agerbae, 2021. "Cryo-EM reveals the architecture of placental malaria VAR2CSA and provides molecular insight into chondroitin sulfate binding," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    2. Chenggong Ji & Hao Shen & Chen Su & Yaxin Li & Shihua Chen & Thomas H. Sharp & Junyu Xiao, 2023. "Plasmodium falciparum has evolved multiple mechanisms to hijack human immunoglobulin M," Nature Communications, Nature, vol. 14(1), pages 1-12, 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. Yuxin Wang & Chen Su & Chenggong Ji & Junyu Xiao, 2024. "CD5L associates with IgM via the J chain," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    2. Elena Ethel Vidal-Calvo & Anne Martin-Salazar & Swati Choudhary & Robert Dagil & Sai Sundar Rajan Raghavan & Lara Duvnjak & Mie Anemone Nordmaj & Thomas Mandel Clausen & Ann Skafte & Jan Oberkofler & , 2024. "Tumor-agnostic cancer therapy using antibodies targeting oncofetal chondroitin sulfate," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Chenggong Ji & Hao Shen & Chen Su & Yaxin Li & Shihua Chen & Thomas H. Sharp & Junyu Xiao, 2023. "Plasmodium falciparum has evolved multiple mechanisms to hijack human immunoglobulin M," Nature Communications, Nature, vol. 14(1), pages 1-12, 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:14:y:2023:i:1:d:10.1038_s41467-023-41838-x. 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.