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== | ==Heterotetramer structure of Region II from Plasmodium vivax Duffy Binding Protein (PvDBP) bound to the ectodomain of the Duffy Antigen Receptor for Chemokines (DARC)== | ||
[[http://www.uniprot.org/uniprot/PVDR_PLAVS PVDR_PLAVS | <StructureSection load='4nuv' size='340' side='right'caption='[[4nuv]], [[Resolution|resolution]] 2.60Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4nuv]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Plasmodium_vivax_Sal-1 Plasmodium vivax Sal-1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NUV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NUV 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]] 2.6Å</td></tr> | |||
<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'>[https://proteopedia.org/fgij/fg.htm?mol=4nuv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nuv OCA], [https://pdbe.org/4nuv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nuv RCSB], [https://www.ebi.ac.uk/pdbsum/4nuv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nuv ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PVDR_PLAVS PVDR_PLAVS] Binds to the human erythrocytes Duffy blood group determinant. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Plasmodium parasites use specialized ligands which bind to red blood cell (RBC) receptors during invasion. Defining the mechanism of receptor recognition is essential for the design of interventions against malaria. Here, we present the structural basis for Duffy antigen (DARC) engagement by P. vivax Duffy binding protein (DBP). We used NMR to map the core region of the DARC ectodomain contacted by the receptor binding domain of DBP (DBP-RII) and solved two distinct crystal structures of DBP-RII bound to this core region of DARC. Isothermal titration calorimetry studies show these structures are part of a multi-step binding pathway, and individual point mutations of residues contacting DARC result in a complete loss of RBC binding by DBP-RII. Two DBP-RII molecules sandwich either one or two DARC ectodomains, creating distinct heterotrimeric and heterotetrameric architectures. The DARC N-terminus forms an amphipathic helix upon DBP-RII binding. The studies reveal a receptor binding pocket in DBP and critical contacts in DARC, reveal novel targets for intervention, and suggest that targeting the critical DARC binding sites will lead to potent disruption of RBC engagement as complex assembly is dependent on DARC binding. These results allow for models to examine inter-species infection barriers, Plasmodium immune evasion mechanisms, P. knowlesi receptor-ligand specificity, and mechanisms of naturally acquired P. vivax immunity. The step-wise binding model identifies a possible mechanism by which signaling pathways could be activated during invasion. It is anticipated that the structural basis of DBP host-cell engagement will enable development of rational therapeutics targeting this interaction. | |||
Red Blood Cell Invasion by Plasmodium vivax: Structural Basis for DBP Engagement of DARC.,Batchelor JD, Malpede BM, Omattage NS, Dekoster GT, Henzler-Wildman KA, Tolia NH PLoS Pathog. 2014 Jan;10(1):e1003869. doi: 10.1371/journal.ppat.1003869. Epub, 2014 Jan 9. PMID:24415938<ref>PMID:24415938</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
< | </div> | ||
<div class="pdbe-citations 4nuv" style="background-color:#fffaf0;"></div> | |||
[[ | ==See Also== | ||
*[[Erythrocyte binding antigen|Erythrocyte binding antigen]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
[[Category: | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Plasmodium vivax Sal-1]] | ||
[[Category: Tolia NH]] | |||
Latest revision as of 06:20, 21 November 2024
Heterotetramer structure of Region II from Plasmodium vivax Duffy Binding Protein (PvDBP) bound to the ectodomain of the Duffy Antigen Receptor for Chemokines (DARC)Heterotetramer structure of Region II from Plasmodium vivax Duffy Binding Protein (PvDBP) bound to the ectodomain of the Duffy Antigen Receptor for Chemokines (DARC)
Structural highlights
FunctionPVDR_PLAVS Binds to the human erythrocytes Duffy blood group determinant. Publication Abstract from PubMedPlasmodium parasites use specialized ligands which bind to red blood cell (RBC) receptors during invasion. Defining the mechanism of receptor recognition is essential for the design of interventions against malaria. Here, we present the structural basis for Duffy antigen (DARC) engagement by P. vivax Duffy binding protein (DBP). We used NMR to map the core region of the DARC ectodomain contacted by the receptor binding domain of DBP (DBP-RII) and solved two distinct crystal structures of DBP-RII bound to this core region of DARC. Isothermal titration calorimetry studies show these structures are part of a multi-step binding pathway, and individual point mutations of residues contacting DARC result in a complete loss of RBC binding by DBP-RII. Two DBP-RII molecules sandwich either one or two DARC ectodomains, creating distinct heterotrimeric and heterotetrameric architectures. The DARC N-terminus forms an amphipathic helix upon DBP-RII binding. The studies reveal a receptor binding pocket in DBP and critical contacts in DARC, reveal novel targets for intervention, and suggest that targeting the critical DARC binding sites will lead to potent disruption of RBC engagement as complex assembly is dependent on DARC binding. These results allow for models to examine inter-species infection barriers, Plasmodium immune evasion mechanisms, P. knowlesi receptor-ligand specificity, and mechanisms of naturally acquired P. vivax immunity. The step-wise binding model identifies a possible mechanism by which signaling pathways could be activated during invasion. It is anticipated that the structural basis of DBP host-cell engagement will enable development of rational therapeutics targeting this interaction. Red Blood Cell Invasion by Plasmodium vivax: Structural Basis for DBP Engagement of DARC.,Batchelor JD, Malpede BM, Omattage NS, Dekoster GT, Henzler-Wildman KA, Tolia NH PLoS Pathog. 2014 Jan;10(1):e1003869. doi: 10.1371/journal.ppat.1003869. Epub, 2014 Jan 9. PMID:24415938[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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