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

Area of Science:

• Parasitology
• Molecular Biology
• Structural Biology

Background:

• Erythrocyte invasion by Plasmodium parasites is crucial for malaria pathogenesis.
• The Plasmodium falciparum Rh5-containing complex (PCRCR) mediates erythrocyte invasion.
• Orthologs of key PCRCR components (PTRAMP, CSS, Ripr) are conserved across Plasmodium species.

Purpose of the Study:

• To investigate conserved features of the PTRAMP, CSS, and Ripr complex across different Plasmodium species.
• To understand the structural basis of the Plasmodium merozoite invasion complex.
• To explore the potential of targeting this complex for broad-spectrum malaria vaccines.

Main Methods:

• Comparative analysis of PTRAMP, CSS, and Ripr orthologs from Plasmodium vivax and Plasmodium knowlesi.
• Biochemical assays to confirm heterodimerization and complex formation.
• Cryo-electron microscopy (Cryo-EM) to visualize the Plasmodium knowlesi PCR complex.

Main Results:

• PTRAMP and CSS form a disulfide-linked heterodimer in P. vivax and P. knowlesi, similar to P. falciparum.
• The Ripr protein binds the C-terminal region of the PTRAMP-CSS heterodimer, forming a conserved PCR complex.
• Cryo-EM revealed a core invasion scaffold, confirming predicted models and highlighting structural conservation.

Conclusions:

• A conserved PCR complex (PTRAMP-CSS-Ripr) acts as a core invasion scaffold across Plasmodium species.
• Cross-reactive antibodies targeting the PCR complex show potential for inhibiting invasion.
• This conserved complex represents a promising target for developing multi-species malaria vaccines.