Journal article
PCRCR complex is essential for invasion of human erythrocytes by Plasmodium falciparum
SW Scally, T Triglia, C Evelyn, BA Seager, M Pasternak, PS Lim, J Healer, ND Geoghegan, A Adair, WH Tham, LF Dagley, KL Rogers, AF Cowman
Nature Microbiology | Published : 2022
Abstract
The most severe form of malaria is caused by Plasmodium falciparum. These parasites invade human erythrocytes, and an essential step in this process involves the ligand PfRh5, which forms a complex with cysteine-rich protective antigen (CyRPA) and PfRh5-interacting protein (PfRipr) (RCR complex) and binds basigin on the host cell. We identified a heteromeric disulfide-linked complex consisting of P. falciparum Plasmodium thrombospondin-related apical merozoite protein (PfPTRAMP) and P. falciparum cysteine-rich small secreted protein (PfCSS) and have shown that it binds RCR to form a pentameric complex, PCRCR. Using P. falciparum lines with conditional knockouts, invasion inhibitory nanobodie..
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Grants
Awarded by Australian Nuclear Science and Technology Organisation
Funding Acknowledgements
We thank Australian Red Cross Blood Service for blood, Walter and Eliza Hall Institute Monoclonal Laboratory for monoclonal antibodies, E. Knuepfer for CRISPR-Cas9 plasmids and M. Mlodzianoski for discussions related to analysis of PAM. Crystallization screening was undertaken at the CSIRO Collaborative Crystallisation Centre (www.csiro.au/C3), Melbourne, Australia. This research was undertaken in part using the MX2 beamline at the Australian Synchrotron, part of the Australian Nuclear Science and Technology Organisation, and made use of the Australian Cancer Research Foundation (ACRF) detector. This work was supported by the National Health and Medical Research Council of Australia (APP1194535 to A.F.C., APP1173049 to S.W.S.) and a Victorian State Government Operational Infrastructure Support grant (institutional grant).