9Q7C
Cryo-electron microscopy structure of PfRIPR bound to monoclonal antibodies RP.092 and RP.052
Summary for 9Q7C
| Entry DOI | 10.2210/pdb9q7c/pdb |
| EMDB information | 72294 |
| Descriptor | Rh5-interacting protein, RP.092 Heavy Chain, RP.092 Light Chain, ... (5 entities in total) |
| Functional Keywords | malaria, ripr, monoclonal antibodies, vaccine, invasion complex, plasmodium falciparum, immune system |
| Biological source | Plasmodium falciparum 3D7 More |
| Total number of polymer chains | 5 |
| Total formula weight | 172377.68 |
| Authors | |
| Primary citation | Williams, B.G.,Barrett, J.R.,Scott, J.B.,Rigby, C.A.,Cagiada, M.,Quinkert, D.,McHugh, K.,Huhn, A.,Burnap, S.A.,Gourjault, C.,Byrne, F.,Raghavan, S.S.R.,Rodrigues, A.,Bergamaschi, L.,Balzarotti, B.,Watson, S.,Miller, N.,King, L.D.W.,Donnellan, F.R.,Gladstone, C.A.,Paterson, J.,Scalabrino, S.,Silk, S.E.,Salkeld, J.,Minassian, A.M.,Skinner, K.,Struwe, W.B.,Deane, C.M.,Reece, S.T.,Ward, A.B.,Draper, S.J. Analysis of monoclonal antibodies against the malaria invasion complex protein RIPR reveals the structural basis for synergistic antibody protection. Immunity, 2026 Cited by PubMed Abstract: 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), but not RIPR or the C-terminal domain (RIPR), synergized to constrain the RIPR-tail conformation. The same antibodies dissociated PTRAMP-CSS from RIPR, thereby enabling anti-RIPR mAbs or anti-CSS single-domain Abs to bind and potentiate anti-RIPR IgG. Addition of these mAbs to IgG from humans immunized with the R78C (RIPR-CyRPA) candidate vaccine enhanced malaria growth inhibition. These data provide a framework to guide next-generation blood-stage malaria vaccine design. PubMed: 42285102DOI: 10.1016/j.immuni.2026.05.012 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.01 Å) |
Structure validation
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