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==Crystal structure of a NHP anti-ZIKV neutralizing antibody rhMZ104-D== | |||
<StructureSection load='8ef0' size='340' side='right'caption='[[8ef0]], [[Resolution|resolution]] 2.55Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8ef0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Macaca_mulatta Macaca mulatta]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8EF0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EF0 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]] 2.55Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8ef0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ef0 OCA], [https://pdbe.org/8ef0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ef0 RCSB], [https://www.ebi.ac.uk/pdbsum/8ef0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ef0 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Zika virus (ZIKV) is an emerging pathogen that causes devastating congenital defects. The overlapping epidemiology and immunologic cross-reactivity between ZIKV and dengue virus (DENV) pose complex challenges to vaccine design, given the potential for antibody-dependent enhancement of disease. Therefore, classification of ZIKV-specific antibody targets is of notable value. From a ZIKV-infected rhesus macaque, we identify ZIKV-reactive B cells and isolate potent neutralizing monoclonal antibodies (mAbs) with no cross-reactivity to DENV. We group these mAbs into four distinct antigenic groups targeting ZIKV-specific cross-protomer epitopes on the envelope glycoprotein. Co-crystal structures of representative mAbs in complex with ZIKV envelope glycoprotein reveal envelope-dimer epitope and unique dimer-dimer epitope targeting. All four specificities are serologically identified in convalescent humans following ZIKV infection, and representative mAbs from all four groups protect against ZIKV replication in mice. These results provide key insights into ZIKV-specific antigenicity and have implications for ZIKV vaccine, diagnostic, and therapeutic development. | |||
Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes.,Sankhala RS, Dussupt V, Donofrio G, Gromowski GD, De La Barrera RA, Larocca RA, Mendez-Rivera L, Lee A, Choe M, Zaky W, Mantus G, Jensen JL, Chen WH, Gohain N, Bai H, McCracken MK, Mason RD, Leggat D, Slike BM, Tran U, Jian N, Abbink P, Peterson R, Mendes EA, Freitas de Oliveira Franca R, Calvet GA, Bispo de Filippis AM, McDermott A, Roederer M, Hernandez M, Albertus A, Davidson E, Doranz BJ, Rolland M, Robb ML, Lynch RM, Barouch DH, Jarman RG, Thomas SJ, Modjarrad K, Michael NL, Krebs SJ, Joyce MG Cell Rep. 2023 Aug 9;42(8):112942. doi: 10.1016/j.celrep.2023.112942. PMID:37561630<ref>PMID:37561630</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8ef0" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Macaca mulatta]] | |||
[[Category: Joyce MG]] | |||
[[Category: Sankhala RS]] | |||
Revision as of 12:08, 30 August 2023
Crystal structure of a NHP anti-ZIKV neutralizing antibody rhMZ104-DCrystal structure of a NHP anti-ZIKV neutralizing antibody rhMZ104-D
Structural highlights
Publication Abstract from PubMedZika virus (ZIKV) is an emerging pathogen that causes devastating congenital defects. The overlapping epidemiology and immunologic cross-reactivity between ZIKV and dengue virus (DENV) pose complex challenges to vaccine design, given the potential for antibody-dependent enhancement of disease. Therefore, classification of ZIKV-specific antibody targets is of notable value. From a ZIKV-infected rhesus macaque, we identify ZIKV-reactive B cells and isolate potent neutralizing monoclonal antibodies (mAbs) with no cross-reactivity to DENV. We group these mAbs into four distinct antigenic groups targeting ZIKV-specific cross-protomer epitopes on the envelope glycoprotein. Co-crystal structures of representative mAbs in complex with ZIKV envelope glycoprotein reveal envelope-dimer epitope and unique dimer-dimer epitope targeting. All four specificities are serologically identified in convalescent humans following ZIKV infection, and representative mAbs from all four groups protect against ZIKV replication in mice. These results provide key insights into ZIKV-specific antigenicity and have implications for ZIKV vaccine, diagnostic, and therapeutic development. Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes.,Sankhala RS, Dussupt V, Donofrio G, Gromowski GD, De La Barrera RA, Larocca RA, Mendez-Rivera L, Lee A, Choe M, Zaky W, Mantus G, Jensen JL, Chen WH, Gohain N, Bai H, McCracken MK, Mason RD, Leggat D, Slike BM, Tran U, Jian N, Abbink P, Peterson R, Mendes EA, Freitas de Oliveira Franca R, Calvet GA, Bispo de Filippis AM, McDermott A, Roederer M, Hernandez M, Albertus A, Davidson E, Doranz BJ, Rolland M, Robb ML, Lynch RM, Barouch DH, Jarman RG, Thomas SJ, Modjarrad K, Michael NL, Krebs SJ, Joyce MG Cell Rep. 2023 Aug 9;42(8):112942. doi: 10.1016/j.celrep.2023.112942. PMID:37561630[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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