| Structural highlights
Function
CYRPA_PLAF7 Essential for the invasion of host erythrocytes by blood stage merozoites (PubMed:22593616, PubMed:25583518, PubMed:27374406, PubMed:28195038, PubMed:28195530). Required for the assembly of the PfRH5 adhesion complex (or invasion complex) composed of CyRPA, RH5 and RIPR at the interface between the merozoite and the host erythrocyte membranes (PubMed:25583518, PubMed:28186186, PubMed:28195038, PubMed:28195530, PubMed:30542156). This facilitates the binding of RH5 to host receptor BSG/basigin, which leads to the establishment of a tight junction between the merozoite and host erythrocyte membranes and allows Ca(2+) release into the erythrocyte (PubMed:27374406, PubMed:28186186, PubMed:30542156).[1] [2] [3] [4] [5] [6] [7]
Publication Abstract from PubMed
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 beta-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.
Structure of the malaria vaccine candidate antigen CyRPA and its complex with a parasite invasion inhibitory antibody.,Favuzza P, Guffart E, Tamborrini M, Scherer B, Dreyer AM, Rufer AC, Erny J, Hoernschemeyer J, Thoma R, Schmid G, Gsell B, Lamelas A, Benz J, Joseph C, Matile H, Pluschke G, Rudolph MG Elife. 2017 Feb 14;6. pii: e20383. doi: 10.7554/eLife.20383. PMID:28195038[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dreyer AM, Matile H, Papastogiannidis P, Kamber J, Favuzza P, Voss TS, Wittlin S, Pluschke G. Passive immunoprotection of Plasmodium falciparum-infected mice designates the CyRPA as candidate malaria vaccine antigen. J Immunol. 2012 Jun 15;188(12):6225-37. PMID:22593616 doi:10.4049/jimmunol.1103177
- ↑ Reddy KS, Amlabu E, Pandey AK, Mitra P, Chauhan VS, Gaur D. Multiprotein complex between the GPI-anchored CyRPA with PfRH5 and PfRipr is crucial for Plasmodium falciparum erythrocyte invasion. Proc Natl Acad Sci U S A. 2015 Jan 27;112(4):1179-84. PMID:25583518 doi:10.1073/pnas.1415466112
- ↑ Volz JC, Yap A, Sisquella X, Thompson JK, Lim NT, Whitehead LW, Chen L, Lampe M, Tham WH, Wilson D, Nebl T, Marapana D, Triglia T, Wong W, Rogers KL, Cowman AF. Essential Role of the PfRh5/PfRipr/CyRPA Complex during Plasmodium falciparum Invasion of Erythrocytes. Cell Host Microbe. 2016 Jul 13;20(1):60-71. PMID:27374406 doi:10.1016/j.chom.2016.06.004
- ↑ Galaway F, Drought LG, Fala M, Cross N, Kemp AC, Rayner JC, Wright GJ. P113 is a merozoite surface protein that binds the N terminus of Plasmodium falciparum RH5. Nat Commun. 2017 Feb 10;8:14333. PMID:28186186 doi:10.1038/ncomms14333
- ↑ Favuzza P, Guffart E, Tamborrini M, Scherer B, Dreyer AM, Rufer AC, Erny J, Hoernschemeyer J, Thoma R, Schmid G, Gsell B, Lamelas A, Benz J, Joseph C, Matile H, Pluschke G, Rudolph MG. Structure of the malaria vaccine candidate antigen CyRPA and its complex with a parasite invasion inhibitory antibody. Elife. 2017 Feb 14;6. pii: e20383. doi: 10.7554/eLife.20383. PMID:28195038 doi:https://dx.doi.org/10.7554/eLife.20383
- ↑ Chen L, Xu Y, Wong W, Thompson JK, Healer J, Goddard-Borger E, Lawrence MC, Cowman AF. Structural basis for inhibition of erythrocyte invasion by antibodies to Plasmodium falciparum protein CyRPA. Elife. 2017 Feb 14;6. pii: e21347. doi: 10.7554/eLife.21347. PMID:28195530 doi:https://dx.doi.org/10.7554/eLife.21347
- ↑ Wong W, Huang R, Menant S, Hong C, Sandow JJ, Birkinshaw RW, Healer J, Hodder AN, Kanjee U, Tonkin CJ, Heckmann D, Soroka V, Sogaard TMM, Jorgensen T, Duraisingh MT, Czabotar PE, de Jongh WA, Tham WH, Webb AI, Yu Z, Cowman AF. Structure of Plasmodium falciparum Rh5-CyRPA-Ripr invasion complex. Nature. 2018 Dec 12. pii: 10.1038/s41586-018-0779-6. doi:, 10.1038/s41586-018-0779-6. PMID:30542156 doi:https://dx.doi.org/10.1038/s41586-018-0779-6
- ↑ Favuzza P, Guffart E, Tamborrini M, Scherer B, Dreyer AM, Rufer AC, Erny J, Hoernschemeyer J, Thoma R, Schmid G, Gsell B, Lamelas A, Benz J, Joseph C, Matile H, Pluschke G, Rudolph MG. Structure of the malaria vaccine candidate antigen CyRPA and its complex with a parasite invasion inhibitory antibody. Elife. 2017 Feb 14;6. pii: e20383. doi: 10.7554/eLife.20383. PMID:28195038 doi:https://dx.doi.org/10.7554/eLife.20383
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