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

## TL;DR

Researchers discovered a conserved protein complex in Plasmodium species that helps the parasite invade red blood cells, which could lead to better malaria vaccines.

## Contribution

The study identifies a conserved complex (PCR) involving PTRAMP, CSS, and Ripr across Plasmodium species and its role in erythrocyte invasion.

## Key findings

- PTRAMP and CSS form a disulfide-linked heterodimer in P. vivax and P. knowlesi.
- The PCR complex with Ripr is conserved across Plasmodium species and is essential for merozoite invasion.
- Cryo-EM visualization of the PCR complex reveals a core invasion scaffold relevant for vaccine development.

## 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 (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.