5o14
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==Co-crystal structure of a cross-reactive bactericidal human antibody targeting meningococcal vaccine antigen factor H binding protein== | ==Co-crystal structure of a cross-reactive bactericidal human antibody targeting meningococcal vaccine antigen factor H binding protein== | ||
| - | <StructureSection load='5o14' size='340' side='right' caption='[[5o14]], [[Resolution|resolution]] 2.19Å' scene=''> | + | <StructureSection load='5o14' size='340' side='right'caption='[[5o14]], [[Resolution|resolution]] 2.19Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5o14]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O14 OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[5o14]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Neisseria_meningitidis_MC58 Neisseria meningitidis MC58]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O14 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5O14 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></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]] 2.195Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=5o14 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o14 OCA], [https://pdbe.org/5o14 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5o14 RCSB], [https://www.ebi.ac.uk/pdbsum/5o14 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5o14 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/FHBP_NEIMB FHBP_NEIMB] A bacterial surface lipoprotein that binds host (human) complement factor H (fH, gene CFH), binding contributes to the avoidance of complement-mediated lysis by N.meningitidis. Binding of fH to the bacteria surface is independent of bacterial sialic acid moieties (PubMed:16751403). fH binding affinity is high enough that it may sequester plasma fH, depleting its circulating levels and de-regulating complement in the host (Probable). This protein induces high levels of bactericidal antibodies in mice (PubMed:12642606, PubMed:15039331, PubMed:15664958, PubMed:21753121, PubMed:23133374).<ref>PMID:12642606</ref> <ref>PMID:15039331</ref> <ref>PMID:15664958</ref> <ref>PMID:16751403</ref> <ref>PMID:21753121</ref> <ref>PMID:23133374</ref> <ref>PMID:19225461</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Data obtained recently in the United Kingdom following a nationwide infant immunization program against serogroup B Neisseria meningitidis (MenB) reported >80% 4CMenB vaccine-mediated protection. Factor H-binding protein (fHbp) is a meningococcal virulence factor and a component of two new MenB vaccines. Here, we investigated the structural bases underlying the fHbp-dependent protective antibody response in humans, which might inform future antigen design efforts. We present the co-crystal structure of a human antibody Fab targeting fHbp. The vaccine-elicited Fab 1A12 is cross-reactive and targets an epitope highly conserved across the repertoire of three naturally occurring fHbp variants. The free Fab structure highlights conformational rearrangements occurring upon antigen binding. Importantly, 1A12 is bactericidal against MenB strains expressing fHbp from all three variants. Our results reveal important immunological features potentially contributing to the broad protection conferred by fHbp vaccination. Our studies fuel the rationale of presenting conserved protein epitopes when developing broadly protective vaccines. | ||
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| + | Crystal structure reveals vaccine elicited bactericidal human antibody targeting a conserved epitope on meningococcal fHbp.,Lopez-Sagaseta J, Beernink PT, Bianchi F, Santini L, Frigimelica E, Lucas AH, Pizza M, Bottomley MJ Nat Commun. 2018 Feb 6;9(1):528. doi: 10.1038/s41467-018-02827-7. PMID:29410413<ref>PMID:29410413</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5o14" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Neisseria meningitidis MC58]] |
| - | [[Category: | + | [[Category: Lopez-Sagaseta J]] |
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Current revision
Co-crystal structure of a cross-reactive bactericidal human antibody targeting meningococcal vaccine antigen factor H binding protein
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