View source for 6rcv


==PfRH5 bound to monoclonal antibodies R5.011 and R5.016==
<StructureSection load='6rcv' size='340' side='right'caption='[[6rcv]], [[Resolution|resolution]] 3.58&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6rcv]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RCV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RCV FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.582&#8491;</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=6rcv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rcv OCA], [https://pdbe.org/6rcv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rcv RCSB], [https://www.ebi.ac.uk/pdbsum/6rcv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rcv ProSAT]</span></td></tr>
</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 ==
The Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) is the leading target for next-generation vaccines against the disease-causing blood-stage of malaria. However, little is known about how human antibodies confer functional immunity against this antigen. We isolated a panel of human monoclonal antibodies (mAbs) against PfRH5 from peripheral blood B cells from vaccinees in the first clinical trial of a PfRH5-based vaccine. We identified a subset of mAbs with neutralizing activity that bind to three distinct sites and another subset of mAbs that are non-functional, or even antagonistic to neutralizing antibodies. We also identify the epitope of a novel group of non-neutralizing antibodies that significantly reduce the speed of red blood cell invasion by the merozoite, thereby potentiating the effect of all neutralizing PfRH5 antibodies as well as synergizing with antibodies targeting other malaria invasion proteins. Our results provide a roadmap for structure-guided vaccine development to maximize antibody efficacy against blood-stage malaria.

Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies.,Alanine DGW, Quinkert D, Kumarasingha R, Mehmood S, Donnellan FR, Minkah NK, Dadonaite B, Diouf A, Galaway F, Silk SE, Jamwal A, Marshall JM, Miura K, Foquet L, Elias SC, Labbe GM, Douglas AD, Jin J, Payne RO, Illingworth JJ, Pattinson DJ, Pulido D, Williams BG, de Jongh WA, Wright GJ, Kappe SHI, Robinson CV, Long CA, Crabb BS, Gilson PR, Higgins MK, Draper SJ Cell. 2019 Jun 13. pii: S0092-8674(19)30553-7. doi: 10.1016/j.cell.2019.05.025. PMID:31204103<ref>PMID:31204103</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6rcv" style="background-color:#fffaf0;"></div>

==See Also==
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Plasmodium falciparum]]
[[Category: Alanine DWG]]
[[Category: Draper SJ]]
[[Category: Higgins MK]]