| Structural highlights
Function
RH5_PLAF7 Essential for the invasion of host erythrocytes by blood stage merozoites (PubMed:25583518, PubMed:27374406, PubMed:25296023, PubMed:22080952, PubMed:18827878, PubMed:19000690, PubMed:31204103, PubMed:28186186, PubMed:28409866). By binding P113 at the surface of the merozoite and human BSG/basigin on the erythrocyte membrane, leads to the establishment of a tight junction between the merozoite and host erythrocyte membranes (PubMed:25583518, PubMed:27374406, PubMed:25296023, PubMed:22080952, PubMed:28186186). In addition, the interaction with BSG results in BSG dimerization which triggers an increase in intracellular Ca(2+) in the erythrocyte (PubMed:27374406, PubMed:28409866). This essential step leads to a rearrangement of the erythrocyte cytoskeleton required for the merozoite invasion (PubMed:28409866).[1] [2] [3] [4] [5] [6] [7] [8] [9]
Publication Abstract from PubMed
Understanding mechanisms of antibody synergy is important for vaccine design and antibody cocktail development. Examples of synergy between antibodies are well-documented, but the mechanisms underlying these relationships often remain poorly understood. The leading blood-stage malaria vaccine candidate, CyRPA, is essential for invasion of Plasmodium falciparum into human erythrocytes. Here we present a panel of anti-CyRPA monoclonal antibodies that strongly inhibit parasite growth in in vitro assays. Structural studies show that growth-inhibitory antibodies bind epitopes on a single face of CyRPA. We also show that pairs of non-competing inhibitory antibodies have strongly synergistic growth-inhibitory activity. These antibodies bind to neighbouring epitopes on CyRPA and form lateral, heterotypic interactions which slow antibody dissociation. We predict that such heterotypic interactions will be a feature of many immune responses. Immunogens which elicit such synergistic antibody mixtures could increase the potency of vaccine-elicited responses to provide robust and long-lived immunity against challenging disease targets.
Heterotypic interactions drive antibody synergy against a malaria vaccine candidate.,Ragotte RJ, Pulido D, Lias AM, Quinkert D, Alanine DGW, Jamwal A, Davies H, Nacer A, Lowe ED, Grime GW, Illingworth JJ, Donat RF, Garman EF, Bowyer PW, Higgins MK, Draper SJ Nat Commun. 2022 Feb 17;13(1):933. doi: 10.1038/s41467-022-28601-4. PMID:35177602[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rodriguez M, Lustigman S, Montero E, Oksov Y, Lobo CA. PfRH5: a novel reticulocyte-binding family homolog of plasmodium falciparum that binds to the erythrocyte, and an investigation of its receptor. PLoS One. 2008 Oct 1;3(10):e3300. PMID:18827878 doi:10.1371/journal.pone.0003300
- ↑ Baum J, Chen L, Healer J, Lopaticki S, Boyle M, Triglia T, Ehlgen F, Ralph SA, Beeson JG, Cowman AF. Reticulocyte-binding protein homologue 5 invasion of human erythrocytes by Plasmodium falciparum. Int J Parasitol. 2009 Feb;39(3):371-80. PMID:19000690 doi:10.1016/j.ijpara.2008.10.006
- ↑ Crosnier C, Bustamante LY, Bartholdson SJ, Bei AK, Theron M, Uchikawa M, Mboup S, Ndir O, Kwiatkowski DP, Duraisingh MT, Rayner JC, Wright GJ. Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum. Nature. 2011 Nov 9;480(7378):534-7. PMID:22080952 doi:10.1038/nature10606
- ↑ Chen L, Xu Y, Healer J, Thompson JK, Smith BJ, Lawrence MC, Cowman AF. Crystal structure of PfRh5, an essential P. falciparum ligand for invasion of human erythrocytes. Elife. 2014 Oct 8;3:e04187. PMID:25296023 doi:10.7554/eLife.04187
- ↑ 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
- ↑ Aniweh Y, Gao X, Hao P, Meng W, Lai SK, Gunalan K, Chu TT, Sinha A, Lescar J, Chandramohanadas R, Li HY, Sze SK, Preiser PR. P. falciparum RH5-Basigin interaction induces changes in the cytoskeleton of the host RBC. Cell Microbiol. 2017 Sep;19(9). PMID:28409866 doi:10.1111/cmi.12747
- ↑ Alanine DGW, Quinkert D, Kumarasingha R, Mehmood S, Donnellan FR, Minkah NK, Dadonaite B, Diouf A, Galaway F, Silk SE, Jamwal A, Marshall JM, Miura K, Foquet L, Elias SC, Labbe GM, Douglas AD, Jin J, Payne RO, Illingworth JJ, Pattinson DJ, Pulido D, Williams BG, de Jongh WA, Wright GJ, Kappe SHI, Robinson CV, Long CA, Crabb BS, Gilson PR, Higgins MK, Draper SJ. Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies. Cell. 2019 Jun 13. pii: S0092-8674(19)30553-7. doi: 10.1016/j.cell.2019.05.025. PMID:31204103 doi:https://dx.doi.org/10.1016/j.cell.2019.05.025
- ↑ Ragotte RJ, Pulido D, Lias AM, Quinkert D, Alanine DGW, Jamwal A, Davies H, Nacer A, Lowe ED, Grime GW, Illingworth JJ, Donat RF, Garman EF, Bowyer PW, Higgins MK, Draper SJ. Heterotypic interactions drive antibody synergy against a malaria vaccine candidate. Nat Commun. 2022 Feb 17;13(1):933. PMID:35177602 doi:10.1038/s41467-022-28601-4
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