9q6b | pdb_00009q6b

Cryo-electron microscopy structure of PfRIPR bound to monoclonal antibodies RP.093, RP.073 and RP.063

Structural highlights

9q6b is a 7 chain structure with sequence from Mus musculus and Plasmodium falciparum 3D7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 2.97Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RH5IP_PLAF7 Essential for the invasion of host erythrocytes by blood stage merozoites (PubMed:21909261, PubMed:25583518, PubMed:27374406, PubMed:27692771). As part of the PfRH5 adhesion complex, facilitates the interaction of RH5 and human BSG required for the Ca(2+) release into the erythrocyte (PubMed:27374406).^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Plasmodium falciparum RH5-interacting protein (RIPR) is central to the essential PTRAMP-CSS-RIPR-CyRPA-RH5 (PCRCR) complex, a leading target of blood-stage malaria vaccines. However, mechanisms whereby anti-RIPR antibodies inhibit parasite invasion are poorly understood. We characterized 83 human IgG monoclonal antibodies (mAbs) from RIPR-vaccinated Kymouse platform mice. Single mAbs had minimal neutralizing activity; however, high-level synergistic inhibition was observed with pools of mAbs targeting the RIPR-tail region. Structural characterization and molecular dynamics simulations of RIPR-tail showed that mAbs targeting epidermal growth factor (EGF)-like domains 6-8 (RIPR(EGF (6-8))), but not RIPR(EGF (9-10)) or the C-terminal domain (RIPR(CTD)), synergized to constrain the RIPR-tail conformation. The same antibodies dissociated PTRAMP-CSS from RIPR, thereby enabling anti-RIPR(EGF (9-10)-CTD) mAbs or anti-CSS single-domain Abs to bind and potentiate anti-RIPR(EGF (6-8)) IgG. Addition of these mAbs to IgG from humans immunized with the R78C (RIPR(EGF (7-8))-CyRPA) candidate vaccine enhanced malaria growth inhibition. These data provide a framework to guide next-generation blood-stage malaria vaccine design.

Analysis of monoclonal antibodies against the malaria invasion complex protein RIPR reveals the structural basis for synergistic antibody protection.,Williams BG, Barrett JR, Scott JB, Rigby CA, Cagiada M, Quinkert D, McHugh K, Huhn A, Burnap SA, Gourjault C, Byrne F, Raghavan SSR, Rodrigues A, Bergamaschi L, Balzarotti B, Watson S, Miller N, King LDW, Donnellan FR, Gladstone CA, Paterson J, Scalabrino S, Silk SE, Salkeld J, Minassian AM, Skinner K, Struwe WB, Deane CM, Reece ST, Ward AB, Draper SJ Immunity. 2026 Jun 12:S1074-7613(26)00223-2. doi: 10.1016/j.immuni.2026.05.012. PMID:42285102^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Chen L, Lopaticki S, Riglar DT, Dekiwadia C, Uboldi AD, Tham WH, O'Neill MT, Richard D, Baum J, Ralph SA, Cowman AF. An EGF-like protein forms a complex with PfRh5 and is required for invasion of human erythrocytes by Plasmodium falciparum. PLoS Pathog. 2011 Sep;7(9):e1002199. PMID:21909261 doi:10.1371/journal.ppat.1002199
↑ 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
↑ Ntege EH, Arisue N, Ito D, Hasegawa T, Palacpac NMQ, Egwang TG, Horii T, Takashima E, Tsuboi T. Identification of Plasmodium falciparum reticulocyte binding protein homologue 5-interacting protein, PfRipr, as a highly conserved blood-stage malaria vaccine candidate. Vaccine. 2016 Nov 4;34(46):5612-5622. PMID:27692771 doi:10.1016/j.vaccine.2016.09.028
↑ Williams BG, Barrett JR, Scott JB, Rigby CA, Cagiada M, Quinkert D, McHugh K, Huhn A, Burnap SA, Gourjault C, Byrne F, Raghavan SSR, Rodrigues A, Bergamaschi L, Balzarotti B, Watson S, Miller N, King LDW, Donnellan FR, Gladstone CA, Paterson J, Scalabrino S, Silk SE, Salkeld J, Minassian AM, Skinner K, Struwe WB, Deane CM, Reece ST, Ward AB, Draper SJ. Analysis of monoclonal antibodies against the malaria invasion complex protein RIPR reveals the structural basis for synergistic antibody protection. Immunity. 2026 Aug 11;59(8):2106-2121.e10. doi: 10.1016/j.immuni.2026.05.012. , Epub 2026 Jun 12. PMID:42285102 doi:https://dx.doi.org/10.1016/j.immuni.2026.05.012

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OCA

[1] Chen L, Lopaticki S, Riglar DT, Dekiwadia C, Uboldi AD, Tham WH, O'Neill MT, Richard D, Baum J, Ralph SA, Cowman AF. An EGF-like protein forms a complex with PfRh5 and is required for invasion of human erythrocytes by Plasmodium falciparum. PLoS Pathog. 2011 Sep;7(9):e1002199. PMID:21909261 doi:10.1371/journal.ppat.1002199

[2] 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

[3] 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

[4] Ntege EH, Arisue N, Ito D, Hasegawa T, Palacpac NMQ, Egwang TG, Horii T, Takashima E, Tsuboi T. Identification of Plasmodium falciparum reticulocyte binding protein homologue 5-interacting protein, PfRipr, as a highly conserved blood-stage malaria vaccine candidate. Vaccine. 2016 Nov 4;34(46):5612-5622. PMID:27692771 doi:10.1016/j.vaccine.2016.09.028

[5] Williams BG, Barrett JR, Scott JB, Rigby CA, Cagiada M, Quinkert D, McHugh K, Huhn A, Burnap SA, Gourjault C, Byrne F, Raghavan SSR, Rodrigues A, Bergamaschi L, Balzarotti B, Watson S, Miller N, King LDW, Donnellan FR, Gladstone CA, Paterson J, Scalabrino S, Silk SE, Salkeld J, Minassian AM, Skinner K, Struwe WB, Deane CM, Reece ST, Ward AB, Draper SJ. Analysis of monoclonal antibodies against the malaria invasion complex protein RIPR reveals the structural basis for synergistic antibody protection. Immunity. 2026 Aug 11;59(8):2106-2121.e10. doi: 10.1016/j.immuni.2026.05.012. , Epub 2026 Jun 12. PMID:42285102 doi:https://dx.doi.org/10.1016/j.immuni.2026.05.012

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9q6b | pdb_00009q6b

Cryo-electron microscopy structure of PfRIPR bound to monoclonal antibodies RP.093, RP.073 and RP.063

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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