8fdd: Difference between revisions
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<StructureSection load='8fdd' size='340' side='right'caption='[[8fdd]], [[Resolution|resolution]] 1.54Å' scene=''> | <StructureSection load='8fdd' size='340' side='right'caption='[[8fdd]], [[Resolution|resolution]] 1.54Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8fdd]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[8fdd]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Plasmodium_falciparum_NF54 Plasmodium falciparum NF54]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8FDD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FDD 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]] 1.54Å</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]] 1.54Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | ||
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</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/ | [https://www.uniprot.org/uniprot/CSP_PLAFO CSP_PLAFO] The circumsporozoite protein is the immunodominant surface antigen on the sporozoite (the infective stage of the malaria parasite that is transmitted from the mosquito to the vertebrate host). | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
IGHV3-33-encoded antibodies are prevalent in the human humoral response against the Plasmodium falciparum circumsporozoite protein (PfCSP). Among VH3-33 antibodies, cross-reactivity between PfCSP major repeat (NANP), minor (NVDP), and junctional (NPDP) motifs is associated with high affinity and potent parasite inhibition. However, the molecular basis of antibody cross-reactivity and the relationship with efficacy remain unresolved. Here, we perform an extensive structure-function characterization of 12 VH3-33 anti-PfCSP monoclonal antibodies (mAbs) with varying degrees of cross-reactivity induced by immunization of mice expressing a human immunoglobulin gene repertoire. We identify residues in the antibody paratope that mediate cross-reactive binding and delineate four distinct epitope conformations induced by antibody binding, with one consistently associated with high protective efficacy and another that confers comparably potent inhibition of parasite liver invasion. Our data show a link between molecular features of cross-reactive VH3-33 mAb binding to PfCSP and mAb potency, relevant for the development of antibody-based interventions against malaria. | |||
Molecular determinants of cross-reactivity and potency by VH3-33 antibodies against the Plasmodium falciparum circumsporozoite protein.,Thai E, Murugan R, Binter S, Burn Aschner C, Prieto K, Kassardjian A, Obraztsova AS, Kang RW, Flores-Garcia Y, Mathis-Torres S, Li K, Horn GQ, Huntwork RHC, Bolscher JM, de Bruijni MHC, Sauerwein R, Dennison SM, Tomaras GD, Zavala F, Kellam P, Wardemann H, Julien JP Cell Rep. 2023 Nov 28;42(11):113330. doi: 10.1016/j.celrep.2023.113330. Epub 2023 , Oct 28. PMID:38007690<ref>PMID:38007690</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 8fdd" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Plasmodium falciparum]] | [[Category: Plasmodium falciparum NF54]] | ||
[[Category: Burn Aschner C]] | [[Category: Burn Aschner C]] | ||
[[Category: Julien JP]] | [[Category: Julien JP]] | ||
Latest revision as of 10:14, 21 November 2024
Crystal structure of Ky15.3 Fab in complex with circumsporozoite protein NPDP peptideCrystal structure of Ky15.3 Fab in complex with circumsporozoite protein NPDP peptide
Structural highlights
FunctionCSP_PLAFO The circumsporozoite protein is the immunodominant surface antigen on the sporozoite (the infective stage of the malaria parasite that is transmitted from the mosquito to the vertebrate host). Publication Abstract from PubMedIGHV3-33-encoded antibodies are prevalent in the human humoral response against the Plasmodium falciparum circumsporozoite protein (PfCSP). Among VH3-33 antibodies, cross-reactivity between PfCSP major repeat (NANP), minor (NVDP), and junctional (NPDP) motifs is associated with high affinity and potent parasite inhibition. However, the molecular basis of antibody cross-reactivity and the relationship with efficacy remain unresolved. Here, we perform an extensive structure-function characterization of 12 VH3-33 anti-PfCSP monoclonal antibodies (mAbs) with varying degrees of cross-reactivity induced by immunization of mice expressing a human immunoglobulin gene repertoire. We identify residues in the antibody paratope that mediate cross-reactive binding and delineate four distinct epitope conformations induced by antibody binding, with one consistently associated with high protective efficacy and another that confers comparably potent inhibition of parasite liver invasion. Our data show a link between molecular features of cross-reactive VH3-33 mAb binding to PfCSP and mAb potency, relevant for the development of antibody-based interventions against malaria. Molecular determinants of cross-reactivity and potency by VH3-33 antibodies against the Plasmodium falciparum circumsporozoite protein.,Thai E, Murugan R, Binter S, Burn Aschner C, Prieto K, Kassardjian A, Obraztsova AS, Kang RW, Flores-Garcia Y, Mathis-Torres S, Li K, Horn GQ, Huntwork RHC, Bolscher JM, de Bruijni MHC, Sauerwein R, Dennison SM, Tomaras GD, Zavala F, Kellam P, Wardemann H, Julien JP Cell Rep. 2023 Nov 28;42(11):113330. doi: 10.1016/j.celrep.2023.113330. Epub 2023 , Oct 28. PMID:38007690[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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