IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-38509-2.html
   My bibliography  Save this article

Structural basis of epitope selectivity and potent protection from malaria by PfCSP antibody L9

Author

Listed:
  • Gregory M. Martin

    (The Scripps Research Institute)

  • Monica L. Fernández-Quintero

    (The University of Innsbruck; Innrain 80-82/III)

  • Wen-Hsin Lee

    (The Scripps Research Institute)

  • Tossapol Pholcharee

    (The Scripps Research Institute
    University of Oxford)

  • Lisa Eshun-Wilson

    (The Scripps Research Institute)

  • Klaus R. Liedl

    (The University of Innsbruck; Innrain 80-82/III)

  • Marie Pancera

    (Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center)

  • Robert A. Seder

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Ian A. Wilson

    (The Scripps Research Institute
    The Skaggs Institute for Chemical Biology, The Scripps Research Institute)

  • Andrew B. Ward

    (The Scripps Research Institute)

Abstract

A primary objective in malaria vaccine design is the generation of high-quality antibody responses against the circumsporozoite protein of the malaria parasite, Plasmodium falciparum (PfCSP). To enable rational antigen design, we solved a cryo-EM structure of the highly potent anti-PfCSP antibody L9 in complex with recombinant PfCSP. We found that L9 Fab binds multivalently to the minor (NPNV) repeat domain, which is stabilized by a unique set of affinity-matured homotypic, antibody-antibody contacts. Molecular dynamics simulations revealed a critical role of the L9 light chain in integrity of the homotypic interface, which likely impacts PfCSP affinity and protective efficacy. These findings reveal the molecular mechanism of the unique NPNV selectivity of L9 and emphasize the importance of anti-homotypic affinity maturation in protective immunity against P. falciparum.

Suggested Citation

  • Gregory M. Martin & Monica L. Fernández-Quintero & Wen-Hsin Lee & Tossapol Pholcharee & Lisa Eshun-Wilson & Klaus R. Liedl & Marie Pancera & Robert A. Seder & Ian A. Wilson & Andrew B. Ward, 2023. "Structural basis of epitope selectivity and potent protection from malaria by PfCSP antibody L9," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38509-2
    DOI: 10.1038/s41467-023-38509-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-38509-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-38509-2?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
    ---><---

    References listed on IDEAS

    as
    1. Susanna Röblitz & Marcus Weber, 2013. "Fuzzy spectral clustering by PCCA+: application to Markov state models and data classification," Advances in Data Analysis and Classification, Springer;German Classification Society - Gesellschaft für Klassifikation (GfKl);Japanese Classification Society (JCS);Classification and Data Analysis Group of the Italian Statistical Society (CLADAG);International Federation of Classification Societies (IFCS), vol. 7(2), pages 147-179, June.
    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. Ravi Kumar Verma & Ara M Abramyan & Mayako Michino & R Benjamin Free & David R Sibley & Jonathan A Javitch & J Robert Lane & Lei Shi, 2018. "The E2.65A mutation disrupts dynamic binding poses of SB269652 at the dopamine D2 and D3 receptors," PLOS Computational Biology, Public Library of Science, vol. 14(1), pages 1-18, January.
    2. Daniel A. Nissley & Yang Jiang & Fabio Trovato & Ian Sitarik & Karthik B. Narayan & Philip To & Yingzi Xia & Stephen D. Fried & Edward P. O’Brien, 2022. "Universal protein misfolding intermediates can bypass the proteostasis network and remain soluble and less functional," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Lin, Yanwen & Hao, Yongchao & Shi, Qiao & Xu, Yihua & Song, Zixuan & Zhou, Ziyue & Fu, Yuequn & Zhang, Zhisen & Wu, Jianyang, 2024. "Enhanced formation of methane hydrates via graphene oxide: Machine learning insights from molecular dynamics simulations," Energy, Elsevier, vol. 289(C).
    4. Ritaban Halder & Daniel A. Nissley & Ian Sitarik & Yang Jiang & Yiyun Rao & Quyen V. Vu & Mai Suan Li & Justin Pritchard & Edward P. O’Brien, 2023. "How soluble misfolded proteins bypass chaperones at the molecular level," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    5. Kalyan S. Chakrabarti & Simon Olsson & Supriya Pratihar & Karin Giller & Kerstin Overkamp & Ko On Lee & Vytautas Gapsys & Kyoung-Seok Ryu & Bert L. Groot & Frank Noé & Stefan Becker & Donghan Lee & Th, 2022. "A litmus test for classifying recognition mechanisms of transiently binding proteins," Nature Communications, Nature, vol. 13(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:14:y:2023:i:1:d:10.1038_s41467-023-38509-2. 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.

    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.