Plasmodium falciparum reticulocyte binding-like homologous protein 5 and cysteine-rich protective antigen invasion protein complex (RH5-CyRPA complex)

The Plasmodium falciparum reticulocyte binding-like homologous protein 5 and cysteine-rich protective antigen invasion protein complex (RH5-CyRPA complex) is an essential, conserved multimeric protein complex required for invasion of human erythrocytes by the malaria parasite P. falciparum[4][8]. RH5 binds directly to the host erythrocyte receptor basigin, while CyRPA mediates assembly of the invasion complex that also includes RH5-Interacting Protein (Ripr)[1][4]. This complex forms at the apical end of the merozoite and is absolutely required for parasite survival[1][5][8]. Disruption of any component blocks invasion and thus parasite growth, making the complex—and especially RH5 and CyRPA—high-priority blood-stage vaccine targets. Antibodies against RH5 or CyRPA block assembly or function of the complex and potently inhibit parasite entry into red blood cells in vitro and in vivo. Both proteins are highly conserved and display minimal polymorphism, supporting their selection as next-generation malaria vaccine candidates[3][4][6][7]. There are currently no approved small molecule therapeutics targeting RH5 or CyRPA; inhibition relies on neutralizing antibodies or immunization approaches under development.

Other names

RH5-CyRPA-Ripr complexRCR-complexPfRH5 (reticulocyte binding-like homologous protein 5)PfCyRPA (cysteine-rich protective antigen)Plasmodium falciparum RH5 and CyRPARH5/CyRPA

Blockade of protein-protein complex formation (RH5/CyRPA/Ripr) to prevent merozoite entry into red blood cells[2][8] Antibodies that bind RH5 or CyRPA sterically hinder interaction with the erythrocyte receptor basigin or with each other, disrupting essential invasion steps[2][7][8]