title: Structural basis for inhibition of erythrocyte invasion by antibodies toPlasmodium falciparumprotein CyRPA.
abstract: Plasmodium falciparumcauses malaria in humans with over 450,000 deaths annually. The asexual blood stage involves invasion of erythrocytes by merozoites, in which they grow and divide to release daughter merozoites, which in turn invade new erythrocytes perpetuating the cycle responsible for malaria. A key step in merozoite invasion is the essential binding of PfRh5/CyRPA/PfRipr complex to basigin, a step linked to the formation of a pore between merozoites and erythrocytes. We show CyRPA interacts directly with PfRh5. An invasion inhibitory monoclonal antibody to CyRPA blocks binding of CyRPA to PfRh5 and complex formation thus illuminating the molecular mechanism for inhibition of parasite growth. We determined the crystal structures of CyRPA alone and in complex with an antibody Fab fragment. CyRPA has a six-bladed β-propeller fold, and we identify the region that interacts with PfRh5. This functionally conserved epitope is a potential target for vaccines againstP. falciparum.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.|Department of Medical Biology, University of Melbourne, Melbourne, Australia.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.|Department of Medical Biology, University of Melbourne, Melbourne, Australia.
authors.forename: Yibin
authors.initials: Y
authors.lastname: Xu
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.|Department of Medical Biology, University of Melbourne, Melbourne, Australia.
authors.forename: Wilson
authors.initials: W
authors.lastname: Wong
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Thompson
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
authors.forename: Julie
authors.initials: J
authors.lastname: Healer
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.|Department of Medical Biology, University of Melbourne, Melbourne, Australia.
authors.forename: Ethan D
authors.initials: ED
authors.lastname: Goddard-Borger
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.|Department of Medical Biology, University of Melbourne, Melbourne, Australia.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Lawrence
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.|Department of Medical Biology, University of Melbourne, Melbourne, Australia.
authors.forename: Alan F
authors.identifier: 0000-0001-5145-9004
authors.initials: AF
authors.lastname: Cowman
mesh_terms: D000913:Antibodies, Protozoan / Q000737:chemistry* / Q000378:metabolism*; D000953:Antigens, Protozoan / Q000737:chemistry* / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D018360:Crystallography, X-Ray; D017780:Malaria Vaccines / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D002352:Carrier Proteins; C000622047:CyRPA protein, Plasmodium falciparum; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C531020:RH5 protein, Plasmodium falciparum; C000622046:Ripr protein, Plasmodium falciparum
keywords: P. falciparum; biochemistry; erythrocyte; human; infectious disease; invasion; malaria; microbiology