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PreprintCited by 10Malaria Research and ControlErythrocyte Function and PathophysiologyToxoplasma gondii Research Studies

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

PTRAMP, CSS and Ripr form a conserved complex required for merozoite invasion of Plasmodium species into erythrocytes

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Seager, Benjamin A., Lim, Pailene S., Lai, Keng Heng, Feufack-Donfack, Lionel Brice, Dass, Sheena, Xiao, Xiao, Jung, Nicolai C., Abraham, Anju, Grigg, Matthew J., Anstey, Nicholas M., William, Timothy, Sattabongkot, Jetsumon, Leis, Andrew, Longley, Rhea J., Duraisingh, Manoj T., Popovici, Jean, Wilson, Danny W., Scally, Stephen W., Cowman, Alan F.·2025·Nature Communications
DOI 10.1101/2025.03.25.644866PMC PMC12916814

Preprint — published as 10.1038/s41467-026-68486-1

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Abstract

Summary: Invasion of erythrocytes by members of the Plasmodium genus is an essential step of the parasite lifecycle, orchestrated by numerous host-parasite interactions. In P. falciparum Rh5, with PfCyRPA, PfRipr, PfCSS, and PfPTRAMP, forms the essential PCRCR complex which binds basigin on the erythrocyte surface. Rh5 is restricted to P. falciparum and its close relatives; however, PTRAMP, CSS and Ripr orthologs are present across the Plasmodium genus. We investigated PTRAMP, CSS and Ripr orthologs from three species to elucidate common features of the complex. Like P. falciparum, PTRAMP and CSS form a disulfide-linked heterodimer in both P. vivax and P. knowlesi with all three species forming a complex (PCR) with Ripr by binding its C-terminal region. Cross-reactive antibodies targeting the PCR complex differentially inhibit merozoite invasion. Cryo-EM visualization of the P. knowlesi PCR complex confirmed predicted models and revealed a core invasion scaffold in Plasmodium spp. with implications for vaccines targeting multiple species of malaria-causing parasites.

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Metadata

Authors
Seager, B. A., Lim, P. S., Lai, K. H., Feufack-Donfack, L. B., Dass, S., Xiao, X., Jung, N. C., Abraham, A., Grigg, M. J., Anstey, N. M., William, T., Sattabongkot, J., Leis, A., Longley, R. J., Duraisingh, M. T., Popovici, J., Wilson, D. W., Scally, S. W., & Cowman, A. F.
Affiliations
  • The University of Melbourne (AU)
  • The University of Adelaide (AU)
  • Institut Pasteur du Cambodge (KH)
  • Harvard University (US)
  • Walter and Eliza Hall Institute of Medical Research (AU)
  • Charles Darwin University (AU)
  • Ministry of Health (MY)
  • Mahidol University (TH)
  • Institut Pasteur (FR)
  • Burnet Institute (AU)
Corresponding author
  • Scally, Stephen W.
  • Cowman, Alan F.
ORCID
Venue
Nature Communications
Publisher
openRxiv
Published
2025-03-25
Volume
17
Issue
1
Pages
1780-1780
ISSN
2041-1723 (ISSN-L)
DOI
10.1101/2025.03.25.644866
PMC
PMC12916814
OpenAlex
W7125707529
Cited by
10
References
1
Citations by year
2026: 5 · 2025: 5
FWCI
32.16
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • Research Square (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion, cc-by)
  • Europe PMC (PubMed Central) (submittedVersion, cc-by-nc-nd)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
  • PubMed Central (submittedVersion, cc-by)
  • HAL (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Bill and Melinda Gates Foundation (INV-074041)
  • Australian Nuclear Science and Technology Organisation
  • Australian Cancer Research Foundation
  • Australian Synchrotron
  • University of Melbourne
  • University of Adelaide
  • National Institutes of Health
  • National Health and Medical Research Council (637406)
  • National Institute of Allergy and Infectious Diseases (R01AI140751)
  • Center for Information Technology (NIH 5R01AI140751)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
  • Health Sciences › Medicine › Physiology (medical) › Erythrocyte Function and Pathophysiology
  • Life Sciences › Immunology and Microbiology › Parasitology › Toxoplasma gondii Research Studies
Keywords
merozoite invasion, Plasmodium, CSS, RH5, CD147, erythrocyte invasion, disulfide-linked heterodimer, cross-reactive antibodies, cryo-EM structure, Plasmodium vivax, Plasmodium knowlesi, Plasmodium falciparum, malaria vaccine targets, host-parasite interactions

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