9q69: Difference between revisions
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==Cryo-electron microscopy structure of PfRIPR bound to monoclonal antibodies RP.047, RP.057 and RP.035== | |||
<StructureSection load='9q69' size='340' side='right'caption='[[9q69]], [[Resolution|resolution]] 3.35Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9q69]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9Q69 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9Q69 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.35Å</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9q69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9q69 OCA], [https://pdbe.org/9q69 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9q69 RCSB], [https://www.ebi.ac.uk/pdbsum/9q69 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9q69 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/RH5IP_PLAF7 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).<ref>PMID:21909261</ref> <ref>PMID:25583518</ref> <ref>PMID:27374406</ref> <ref>PMID:27692771</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:42285102</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 9q69" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Plasmodium falciparum 3D7]] | |||
[[Category: Barrett JR]] | |||
[[Category: Ward AB]] | |||