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| | ==Crystal structure of PfEBA-175 RII in complex with a Fab fragment from inhibitory antibody R217== | | ==Crystal structure of PfEBA-175 RII in complex with a Fab fragment from inhibitory antibody R217== |
| - | <StructureSection load='4qex' size='340' side='right' caption='[[4qex]], [[Resolution|resolution]] 4.50Å' scene=''> | + | <StructureSection load='4qex' size='340' side='right'caption='[[4qex]], [[Resolution|resolution]] 4.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4qex]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4k4m 4k4m]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QEX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QEX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4qex]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4k4m 4k4m]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QEX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QEX FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4k2u|4k2u]]</td></tr> | + | </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=4qex FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qex OCA], [https://pdbe.org/4qex PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qex RCSB], [https://www.ebi.ac.uk/pdbsum/4qex PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qex ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4qex FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qex OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qex RCSB], [http://www.ebi.ac.uk/pdbsum/4qex PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q05644_PLAFA Q05644_PLAFA] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4qex" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Antibody 3D structures|Antibody 3D structures]] |
| | + | *[[Erythrocyte binding antigen|Erythrocyte binding antigen]] |
| | + | *[[3D structures of non-human antibody|3D structures of non-human antibody]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
| - | [[Category: Chen, E]] | + | [[Category: Plasmodium falciparum]] |
| - | [[Category: Paing, M M]] | + | [[Category: Chen E]] |
| - | [[Category: Salinas, N]] | + | [[Category: Paing MM]] |
| - | [[Category: Sim, B K]] | + | [[Category: Salinas N]] |
| - | [[Category: Tolia, N H]]
| + | [[Category: Sim BK]] |
| - | [[Category: Adhesion]] | + | [[Category: Tolia NH]] |
| - | [[Category: Antibody]] | + | |
| - | [[Category: Cell adhesion]]
| + | |
| - | [[Category: Cell surface]]
| + | |
| - | [[Category: Extrecellular]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Immunity]]
| + | |
| - | [[Category: Immunoglobulin domain]]
| + | |
| - | [[Category: Invasion]]
| + | |
| - | [[Category: Ligand]]
| + | |
| - | [[Category: Pfeba-175]]
| + | |
| - | [[Category: Receptor]]
| + | |
| Structural highlights
Function
Q05644_PLAFA
Publication Abstract from PubMed
Disrupting erythrocyte invasion by Plasmodium falciparum is an attractive approach to combat malaria. P. falciparum EBA-175 (PfEBA-175) engages the host receptor Glycophorin A (GpA) during invasion and is a leading vaccine candidate. Antibodies that recognize PfEBA-175 can prevent parasite growth, although not all antibodies are inhibitory. Here, using x-ray crystallography, small-angle x-ray scattering and functional studies, we report the structural basis and mechanism for inhibition by two PfEBA-175 antibodies. Structures of each antibody in complex with the PfEBA-175 receptor binding domain reveal that the most potent inhibitory antibody, R217, engages critical GpA binding residues and the proposed dimer interface of PfEBA-175. A second weakly inhibitory antibody, R218, binds to an asparagine-rich surface loop. We show that the epitopes identified by structural studies are critical for antibody binding. Together, the structural and mapping studies reveal distinct mechanisms of action, with R217 directly preventing receptor binding while R218 allows for receptor binding. Using a direct receptor binding assay we show R217 directly blocks GpA engagement while R218 does not. Our studies elaborate on the complex interaction between PfEBA-175 and GpA and highlight new approaches to targeting the molecular mechanism of P. falciparum invasion of erythrocytes. The results suggest studies aiming to improve the efficacy of blood-stage vaccines, either by selecting single or combining multiple parasite antigens, should assess the antibody response to defined inhibitory epitopes as well as the response to the whole protein antigen. Finally, this work demonstrates the importance of identifying inhibitory-epitopes and avoiding decoy-epitopes in antibody-based therapies, vaccines and diagnostics.
Structural and Functional Basis for Inhibition of Erythrocyte Invasion by Antibodies that Target Plasmodium falciparum EBA-175.,Chen E, Paing MM, Salinas N, Sim BK, Tolia NH PLoS Pathog. 2013 May;9(5):e1003390. doi: 10.1371/journal.ppat.1003390. Epub 2013, May 23. PMID:23717209[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Chen E, Paing MM, Salinas N, Sim BK, Tolia NH. Structural and Functional Basis for Inhibition of Erythrocyte Invasion by Antibodies that Target Plasmodium falciparum EBA-175. PLoS Pathog. 2013 May;9(5):e1003390. doi: 10.1371/journal.ppat.1003390. Epub 2013, May 23. PMID:23717209 doi:10.1371/journal.ppat.1003390
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