Structure of the malaria vaccine candidate antigen CyRPA and its complex with a parasite invasion inhibitory antibody
- Swiss Tropical and Public Health Institute, Switzerland
- Roche Innovation Center Basel, Switzerland
- Instituto de Ecología A.C., Mexico
Abstract
Invasion of erythrocytes by Plasmodial merozoites is a composite process involving the interplay of several proteins. Among them, the Plasmodium falciparum Cysteine-Rich Protective Antigen (PfCyRPA) is a crucial component of a ternary complex, including Reticulocyte binding-like Homologous protein 5 (PfRH5) and the RH5-interacting protein (PfRipr), essential for erythrocyte invasion. Here we present the crystal structure of PfCyRPA and of its complex with the antigen-binding fragment of a parasite growth inhibitory antibody. While PfCyRPA adopts a 6-bladed β-propeller structure with similarity to the classic sialidase fold, it possesses no sialidase activity, indicating that it fulfills a non-enzymatic function. Characterization of the epitope recognized by protective antibodies will facilitate design of peptidomimetics that focus vaccine responses on protective epitopes. Both in vitro and in vivo anti-PfCyRPA and anti-PfRH5 antibodies showed more potent parasite growth inhibitory activity in combination than on their own, supporting a combined delivery of PfCyRPA and PfRH5 in vaccines.
Data availability
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Crystal Structure of Fab c12Publicly available at the RCSB Protein Data Bank (accession no: 5EZI).
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Crystal Structure of Fab c12Publicly available at the RCSB Protein Data Bank (accession no: 5EZL).
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Crystal Structure of Fab c12Publicly available at the RCSB Protein Data Bank (accession no: 5EZJ).
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Crystal Structure of PfCyRPAPublicly available at the RCSB Protein Data Bank (accession no: 5EZN).
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Crystal Structure of PfCyRPAPublicly available at the RCSB Protein Data Bank (accession no: 5EZO).
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PlasmoDB: a functional genomic database for malaria parasites.The data at this site is provided freely for public use.
Article and author information
Author details
Funding
Uniscientia Stiftung
- Gerd Pluschke
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All procedures involving living animals were performed in strict accordance with the Rules and Regulations for the Protection of Animal Rights (Tierschutzverordnung) of the Swiss Federal Food Safety and Veterinary Office. The protocol was granted ethical approval by the Veterinary Office of the county of Basel-Stadt, Switzerland (Permit Numbers: 2375 and 2303).
Copyright
© 2017, Favuzza et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Structure of the malaria vaccine candidate antigen CyRPA and its complex with a parasite invasion inhibitory antibody
eLife 6:e20383.
https://doi.org/10.7554/eLife.20383
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