7pi3: Difference between revisions
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==PfCyRPA bound to Fab fragments from monoclonal antibodies Cy.003, Cy.004 and Cy.007== | ==PfCyRPA bound to Fab fragments from monoclonal antibodies Cy.003, Cy.004 and Cy.007== | ||
<StructureSection load='7pi3' size='340' side='right'caption='[[7pi3]]' scene=''> | <StructureSection load='7pi3' size='340' side='right'caption='[[7pi3]], [[Resolution|resolution]] 3.27Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PI3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PI3 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7pi3]] is a 28 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] 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=7PI3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PI3 FirstGlance]. <br> | ||
</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=7pi3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pi3 OCA], [https://pdbe.org/7pi3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pi3 RCSB], [https://www.ebi.ac.uk/pdbsum/7pi3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pi3 ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.269Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></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=7pi3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pi3 OCA], [https://pdbe.org/7pi3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pi3 RCSB], [https://www.ebi.ac.uk/pdbsum/7pi3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pi3 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/CYRPA_PLAF7 CYRPA_PLAF7] Essential for the invasion of host erythrocytes by blood stage merozoites (PubMed:22593616, PubMed:25583518, PubMed:27374406, PubMed:28195530, PubMed:28195038). 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:28195530, PubMed:28195038, 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).<ref>PMID:22593616</ref> <ref>PMID:25583518</ref> <ref>PMID:27374406</ref> <ref>PMID:28186186</ref> <ref>PMID:28195038</ref> <ref>PMID:28195530</ref> <ref>PMID:30542156</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:35177602</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7pi3" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Gallus gallus]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Plasmodium falciparum 3D7]] | |||
[[Category: Higgins MK]] | [[Category: Higgins MK]] | ||
[[Category: Ragotte RJ]] | [[Category: Ragotte RJ]] | ||