7qqb: Difference between revisions
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<StructureSection load='7qqb' size='340' side='right'caption='[[7qqb]], [[Resolution|resolution]] 2.60Å' scene=''> | <StructureSection load='7qqb' size='340' side='right'caption='[[7qqb]], [[Resolution|resolution]] 2.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7qqb]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[7qqb]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Orthohantavirus_puumalaense Orthohantavirus puumalaense]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QQB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QQB 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> | </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=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | ||
| Line 10: | Line 10: | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/A0A0B4U5I0_9VIRU A0A0B4U5I0_9VIRU] [https://www.uniprot.org/uniprot/A0A6M3W7M6_9VIRU A0A6M3W7M6_9VIRU] | [https://www.uniprot.org/uniprot/A0A0B4U5I0_9VIRU A0A0B4U5I0_9VIRU] [https://www.uniprot.org/uniprot/A0A6M3W7M6_9VIRU A0A6M3W7M6_9VIRU] | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Emerging rodent-borne hantaviruses cause severe diseases in humans with no approved vaccines or therapeutics. We recently isolated a monoclonal broadly neutralizing antibody (nAb) from a Puumala virus-experienced human donor. Here, we report its structure bound to its target, the Gn/Gc glycoprotein heterodimer comprising the viral fusion complex. The structure explains the broad activity of the nAb: It recognizes conserved Gc fusion loop sequences and the main chain of variable Gn sequences, thereby straddling the Gn/Gc heterodimer and locking it in its prefusion conformation. We show that the nAb's accelerated dissociation from the divergent Andes virus Gn/Gc at endosomal acidic pH limits its potency against this highly lethal virus and correct this liability by engineering an optimized variant that sets a benchmark as a candidate pan-hantavirus therapeutic. | |||
Structural and mechanistic basis of neutralization by a pan-hantavirus protective antibody.,Mittler E, Serris A, Esterman ES, Florez C, Polanco LC, O'Brien CM, Slough MM, Tynell J, Groning R, Sun Y, Abelson DM, Wec AZ, Haslwanter D, Keller M, Ye C, Bakken RR, Jangra RK, Dye JM, Ahlm C, Rappazzo CG, Ulrich RG, Zeitlin L, Geoghegan JC, Bradfute SB, Sidoli S, Forsell MNE, Strandin T, Rey FA, Herbert AS, Walker LM, Chandran K, Guardado-Calvo P Sci Transl Med. 2023 Jun 14;15(700):eadg1855. doi: 10.1126/scitranslmed.adg1855. , Epub 2023 Jun 14. PMID:37315110<ref>PMID:37315110</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7qqb" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Orthohantavirus puumalaense]] | ||
[[Category: Guardado-Calvo P]] | [[Category: Guardado-Calvo P]] | ||
[[Category: Rey FA]] | [[Category: Rey FA]] | ||
[[Category: Serris A]] | [[Category: Serris A]] | ||
Latest revision as of 14:24, 23 October 2024
Crystal structure of the envelope glycoprotein complex of Puumala virus in complex with the scFv fragment of the broadly neutralizing human antibody ADI-42898Crystal structure of the envelope glycoprotein complex of Puumala virus in complex with the scFv fragment of the broadly neutralizing human antibody ADI-42898
Structural highlights
FunctionA0A0B4U5I0_9VIRU A0A6M3W7M6_9VIRU Publication Abstract from PubMedEmerging rodent-borne hantaviruses cause severe diseases in humans with no approved vaccines or therapeutics. We recently isolated a monoclonal broadly neutralizing antibody (nAb) from a Puumala virus-experienced human donor. Here, we report its structure bound to its target, the Gn/Gc glycoprotein heterodimer comprising the viral fusion complex. The structure explains the broad activity of the nAb: It recognizes conserved Gc fusion loop sequences and the main chain of variable Gn sequences, thereby straddling the Gn/Gc heterodimer and locking it in its prefusion conformation. We show that the nAb's accelerated dissociation from the divergent Andes virus Gn/Gc at endosomal acidic pH limits its potency against this highly lethal virus and correct this liability by engineering an optimized variant that sets a benchmark as a candidate pan-hantavirus therapeutic. Structural and mechanistic basis of neutralization by a pan-hantavirus protective antibody.,Mittler E, Serris A, Esterman ES, Florez C, Polanco LC, O'Brien CM, Slough MM, Tynell J, Groning R, Sun Y, Abelson DM, Wec AZ, Haslwanter D, Keller M, Ye C, Bakken RR, Jangra RK, Dye JM, Ahlm C, Rappazzo CG, Ulrich RG, Zeitlin L, Geoghegan JC, Bradfute SB, Sidoli S, Forsell MNE, Strandin T, Rey FA, Herbert AS, Walker LM, Chandran K, Guardado-Calvo P Sci Transl Med. 2023 Jun 14;15(700):eadg1855. doi: 10.1126/scitranslmed.adg1855. , Epub 2023 Jun 14. PMID:37315110[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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