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| | ==Crystal structure of Apical Membrane Antigen 1 from Plasmodium Knowlesi in complex with an invasion inhibitory antibody== | | ==Crystal structure of Apical Membrane Antigen 1 from Plasmodium Knowlesi in complex with an invasion inhibitory antibody== |
| - | <StructureSection load='4uao' size='340' side='right' caption='[[4uao]], [[Resolution|resolution]] 3.10Å' scene=''> | + | <StructureSection load='4uao' size='340' side='right'caption='[[4uao]], [[Resolution|resolution]] 3.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4uao]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Plakn Plakn] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UAO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UAO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4uao]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_knowlesi Plasmodium knowlesi] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UAO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UAO FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4uv6|4uv6]]</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]] 3.1Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PKH_093110 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5850 PLAKN])</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=4uao FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uao OCA], [https://pdbe.org/4uao PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4uao RCSB], [https://www.ebi.ac.uk/pdbsum/4uao PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4uao 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=4uao FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uao OCA], [http://pdbe.org/4uao PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4uao RCSB], [http://www.ebi.ac.uk/pdbsum/4uao PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4uao ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/A0A384KGX8_PLAKH A0A384KGX8_PLAKH] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Plakn]] | + | [[Category: Large Structures]] |
| | + | [[Category: Plasmodium knowlesi]] |
| | [[Category: Rattus norvegicus]] | | [[Category: Rattus norvegicus]] |
| - | [[Category: Bentley, G A]] | + | [[Category: Bentley GA]] |
| - | [[Category: Normand, B Vulliez-Le]]
| + | [[Category: Saul FA]] |
| - | [[Category: Saul, F A]] | + | [[Category: Vulliez-Le Normand B]] |
| - | [[Category: Cell invasion]] | + | |
| - | [[Category: Invasion inhibitory antibody]]
| + | |
| - | [[Category: Malaria]]
| + | |
| Structural highlights
Function
A0A384KGX8_PLAKH
Publication Abstract from PubMed
The malaria parasite Plasmodium knowlesi, previously associated only with infection of macaques, is now known to infect humans as well and has become a significant public health problem in Southeast Asia. This species should therefore be targeted in vaccine and therapeutic strategies against human malaria. Apical Membrane Antigen 1 (AMA1), which plays a role in Plasmodium merozoite invasion of the erythrocyte, is currently being pursued in human vaccine trials against P. falciparum. Recent vaccine trials in macaques using the P. knowlesi orthologue PkAMA1 have shown that it protects against infection by this parasite species and thus should be developed for human vaccination as well. Here, we present the crystal structure of Domains 1 and 2 of the PkAMA1 ectodomain, and of its complex with the invasion-inhibitory monoclonal antibody R31C2. The Domain 2 (D2) loop, which is displaced upon binding the Rhoptry Neck Protein 2 (RON2) receptor, makes significant contacts with the antibody. R31C2 inhibits binding of the Rhoptry Neck Protein 2 (RON2) receptor by steric blocking of the hydrophobic groove and by preventing the displacement of the D2 loop which is essential for exposing the complete binding site on AMA1. R31C2 recognizes a non-polymorphic epitope and should thus be cross-strain reactive. PkAMA1 is much less polymorphic than the P. falciparum and P. vivax orthologues. Unlike these two latter species, there are no polymorphic sites close to the RON2-binding site of PkAMA1, suggesting that P. knowlesi has not developed a mechanism of immune escape from the host's humoral response to AMA1.
Crystal Structure of Plasmodium knowlesi Apical Membrane Antigen 1 and Its Complex with an Invasion-Inhibitory Monoclonal Antibody.,Vulliez-Le Normand B, Faber BW, Saul FA, van der Eijk M, Thomas AW, Singh B, Kocken CH, Bentley GA PLoS One. 2015 Apr 17;10(4):e0123567. doi: 10.1371/journal.pone.0123567., eCollection 2015. PMID:25886591[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Vulliez-Le Normand B, Faber BW, Saul FA, van der Eijk M, Thomas AW, Singh B, Kocken CH, Bentley GA. Crystal Structure of Plasmodium knowlesi Apical Membrane Antigen 1 and Its Complex with an Invasion-Inhibitory Monoclonal Antibody. PLoS One. 2015 Apr 17;10(4):e0123567. doi: 10.1371/journal.pone.0123567., eCollection 2015. PMID:25886591 doi:http://dx.doi.org/10.1371/journal.pone.0123567
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