6b08: Difference between revisions
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==Crystal structure of Pfs25 in complex with the transmission blocking antibody 1276== | ==Crystal structure of Pfs25 in complex with the transmission blocking antibody 1276== | ||
<StructureSection load='6b08' size='340' side='right' caption='[[6b08]], [[Resolution|resolution]] 2.20Å' scene=''> | <StructureSection load='6b08' size='340' side='right'caption='[[6b08]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6b08]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B08 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6b08]] is a 3 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=6B08 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6B08 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6b08 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b08 OCA], [https://pdbe.org/6b08 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6b08 RCSB], [https://www.ebi.ac.uk/pdbsum/6b08 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6b08 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/OS25_PLAFO OS25_PLAFO] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The Plasmodium falciparum Pfs25 protein (Pfs25) is a leading malaria transmission-blocking vaccine antigen. Pfs25 vaccination is intended to elicit antibodies that inhibit parasite development when ingested by Anopheles mosquitoes during blood meals. The Pfs25 three-dimensional structure has remained elusive, hampering a molecular understanding of its function and limiting immunogen design. We report six crystal structures of Pfs25 in complex with antibodies elicited by immunization via Pfs25 virus-like particles in human immunoglobulin loci transgenic mice. Our structural findings reveal the fine specificities associated with two distinct immunogenic sites on Pfs25. Importantly, one of these sites broadly overlaps with the epitope of the well-known 4B7 mouse antibody, which can be targeted simultaneously by antibodies that target a non-overlapping site to additively increase parasite inhibition. Our molecular characterization of inhibitory antibodies informs on the natural disposition of Pfs25 on the surface of ookinetes and provides the structural blueprints to design next-generation immunogens. | |||
Molecular definition of multiple sites of antibody inhibition of malaria transmission-blocking vaccine antigen Pfs25.,Scally SW, McLeod B, Bosch A, Miura K, Liang Q, Carroll S, Reponen S, Nguyen N, Giladi E, Ramisch S, Yusibov V, Bradley A, Lemiale F, Schief WR, Emerling D, Kellam P, King CR, Julien JP Nat Commun. 2017 Nov 16;8(1):1568. doi: 10.1038/s41467-017-01924-3. PMID:29146922<ref>PMID:29146922</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6b08" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[3D structures of human antibody|3D structures of human antibody]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Plasmodium falciparum]] | ||
[[Category: | [[Category: Bosch A]] | ||
[[Category: | [[Category: Julien JP]] | ||
[[Category: | [[Category: King CR]] | ||
[[Category: | [[Category: McLeod B]] | ||
[[Category: | [[Category: Scally SW]] | ||
Latest revision as of 17:29, 4 October 2023
Crystal structure of Pfs25 in complex with the transmission blocking antibody 1276Crystal structure of Pfs25 in complex with the transmission blocking antibody 1276
Structural highlights
FunctionPublication Abstract from PubMedThe Plasmodium falciparum Pfs25 protein (Pfs25) is a leading malaria transmission-blocking vaccine antigen. Pfs25 vaccination is intended to elicit antibodies that inhibit parasite development when ingested by Anopheles mosquitoes during blood meals. The Pfs25 three-dimensional structure has remained elusive, hampering a molecular understanding of its function and limiting immunogen design. We report six crystal structures of Pfs25 in complex with antibodies elicited by immunization via Pfs25 virus-like particles in human immunoglobulin loci transgenic mice. Our structural findings reveal the fine specificities associated with two distinct immunogenic sites on Pfs25. Importantly, one of these sites broadly overlaps with the epitope of the well-known 4B7 mouse antibody, which can be targeted simultaneously by antibodies that target a non-overlapping site to additively increase parasite inhibition. Our molecular characterization of inhibitory antibodies informs on the natural disposition of Pfs25 on the surface of ookinetes and provides the structural blueprints to design next-generation immunogens. Molecular definition of multiple sites of antibody inhibition of malaria transmission-blocking vaccine antigen Pfs25.,Scally SW, McLeod B, Bosch A, Miura K, Liang Q, Carroll S, Reponen S, Nguyen N, Giladi E, Ramisch S, Yusibov V, Bradley A, Lemiale F, Schief WR, Emerling D, Kellam P, King CR, Julien JP Nat Commun. 2017 Nov 16;8(1):1568. doi: 10.1038/s41467-017-01924-3. PMID:29146922[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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