title: P113 is a merozoite surface protein that binds the N terminus of Plasmodium falciparum RH5.
abstract: Invasion of erythrocytes by Plasmodium falciparum merozoites is necessary for malaria pathogenesis and is therefore a primary target for vaccine development. RH5 is a leading subunit vaccine candidate because anti-RH5 antibodies inhibit parasite growth and the interaction with its erythrocyte receptor basigin is essential for invasion. RH5 is secreted, complexes with other parasite proteins including CyRPA and RIPR, and contains a conserved N-terminal region (RH5Nt) of unknown function that is cleaved from the native protein. Here, we identify P113 as a merozoite surface protein that directly interacts with RH5Nt. Using recombinant proteins and a sensitive protein interaction assay, we establish the binding interdependencies of all the other known RH5 complex components and conclude that the RH5Nt-P113 interaction provides a releasable mechanism for anchoring RH5 to the merozoite surface. We exploit these findings to design a chemically synthesized peptide corresponding to RH5Nt, which could contribute to a cost-effective malaria vaccine.
authors.affiliation: Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
authors.forename: Francis
authors.initials: F
authors.lastname: Galaway
authors.forename: Laura G
authors.initials: LG
authors.lastname: Drought
authors.affiliation: Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Fala
authors.forename: Nadia
authors.initials: N
authors.lastname: Cross
authors.forename: Alison C
authors.initials: AC
authors.lastname: Kemp
authors.forename: Julian C
authors.initials: JC
authors.lastname: Rayner
authors.affiliation: Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Wright
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology / Q000378:metabolism; D000953:Antigens, Protozoan / Q000276:immunology / Q000378:metabolism; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism*; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology; D057809:HEK293 Cells; D006801:Humans; D017780:Malaria Vaccines / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D008565:Membrane Proteins / Q000378:metabolism*; D052940:Merozoites / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D015800:Protozoan Proteins / Q000378:metabolism*
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D002352:Carrier Proteins; D017780:Malaria Vaccines; D008565:Membrane Proteins; D015800:Protozoan Proteins; C531020:RH5 protein, Plasmodium falciparum