PTRAMP, CSS and Ripr form a conserved complex required for merozoite invasion of Plasmodium species into erythrocytes
Issued Date
2026-12-01
Resource Type
eISSN
20411723
Scopus ID
2-s2.0-105030470914
Pubmed ID
41587959
Journal Title
Nature Communications
Volume
17
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Nature Communications Vol.17 No.1 (2026)
Suggested Citation
Seager B.A., Lim P.S., Xiao X., Lai K.H., Feufack-Donfack L.B., Dass S., 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., Cowman A.F., Scally S.W. PTRAMP, CSS and Ripr form a conserved complex required for merozoite invasion of Plasmodium species into erythrocytes. Nature Communications Vol.17 No.1 (2026). doi:10.1038/s41467-026-68486-1 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/115396
Title
PTRAMP, CSS and Ripr form a conserved complex required for merozoite invasion of Plasmodium species into erythrocytes
Author's Affiliation
University of Melbourne
Université Paris Cité
The University of Adelaide
Harvard T.H. Chan School of Public Health
Walter and Eliza Hall Institute of Medical Research
Faculty of Tropical Medicine, Mahidol University
Menzies School of Health Research
Burnet Institute
Kementerian Kesihatan Malaysia
Institut Pasteur du Cambodge
Infectious Diseases Society Kota Kinabalu Sabah-Menzies School of Health Research Program
Université Paris Cité
The University of Adelaide
Harvard T.H. Chan School of Public Health
Walter and Eliza Hall Institute of Medical Research
Faculty of Tropical Medicine, Mahidol University
Menzies School of Health Research
Burnet Institute
Kementerian Kesihatan Malaysia
Institut Pasteur du Cambodge
Infectious Diseases Society Kota Kinabalu Sabah-Menzies School of Health Research Program
Corresponding Author(s)
Other Contributor(s)
Abstract
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 with Ripr by binding its C-terminal region, termed the PTRAMP-CSS-Ripr (PCR) complex. Cross-reactive antibodies targeting the PCR complex differentially inhibit merozoite invasion. The crystal structure of a cross-reactive antibody reveals an inhibitory epitope on the C-terminal tail of PvRipr. Cryo-EM visualization of the P. knowlesi PCR complex confirms predicted models and demonstrates a core invasion scaffold in Plasmodium spp. with implications for vaccines targeting multiple species of malaria-causing parasites.