7phu: Difference between revisions
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==== | ==PfRH5 bound to monoclonal antibody R5.015 and R5.016 Fab fragments== | ||
<StructureSection load='7phu' size='340' side='right'caption='[[7phu]]' scene=''> | <StructureSection load='7phu' size='340' side='right'caption='[[7phu]], [[Resolution|resolution]] 2.53Å' 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= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7phu]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=7PHU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PHU 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=7phu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7phu OCA], [https://pdbe.org/7phu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7phu RCSB], [https://www.ebi.ac.uk/pdbsum/7phu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7phu 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]] 2.53Å</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=7phu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7phu OCA], [https://pdbe.org/7phu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7phu RCSB], [https://www.ebi.ac.uk/pdbsum/7phu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7phu ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/RH5_PLAF7 RH5_PLAF7] Essential for the invasion of host erythrocytes by blood stage merozoites (PubMed:18827878, PubMed:19000690, PubMed:22080952, PubMed:25296023, PubMed:25583518, PubMed:27374406, PubMed:28186186, PubMed:28409866, PubMed:31204103). 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:22080952, PubMed:25296023, PubMed:25583518, PubMed:27374406, 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).<ref>PMID:18827878</ref> <ref>PMID:19000690</ref> <ref>PMID:22080952</ref> <ref>PMID:25296023</ref> <ref>PMID:25583518</ref> <ref>PMID:27374406</ref> <ref>PMID:28186186</ref> <ref>PMID:28409866</ref> <ref>PMID:31204103</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 7phu" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Plasmodium falciparum 3D7]] | ||
[[Category: Higgins MK]] | |||
[[Category: Ragotte RJ]] | |||