6fla: Difference between revisions
New page: '''Unreleased structure''' The entry 6fla is ON HOLD Authors: Flanagan, A., Renner, M., Grimes, J.M. Description: 3H5 Fab bound to EDIII of DenV 2 Xtal form 1 [[Category: Unreleased St... |
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==3H5 Fab bound to EDIII of DenV 2 Xtal form 1== | |||
<StructureSection load='6fla' size='340' side='right'caption='[[6fla]], [[Resolution|resolution]] 2.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6fla]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Dengue_virus_2 Dengue virus 2] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FLA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FLA 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]] 2.9Å</td></tr> | |||
<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=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=6fla FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fla OCA], [https://pdbe.org/6fla PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fla RCSB], [https://www.ebi.ac.uk/pdbsum/6fla PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fla ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/W5RZ25_9FLAV W5RZ25_9FLAV] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Dengue virus is a major pathogen, and severe infections can lead to life-threatening dengue hemorrhagic fever. Dengue virus exists as four serotypes, and dengue hemorrhagic fever is often associated with secondary heterologous infections. Antibody-dependent enhancement (ADE) may drive higher viral loads in these secondary infections and is purported to result from antibodies that recognize dengue virus but fail to fully neutralize it. Here we characterize two antibodies, 2C8 and 3H5, that bind to the envelope protein. Antibody 3H5 is highly unusual as it not only is potently neutralizing but also promotes little if any ADE, whereas antibody 2C8 has strong capacity to promote ADE. We show that 3H5 shows resilient binding in endosomal pH conditions and neutralizes at low occupancy. Immunocomplexes of 3H5 and dengue virus do not efficiently interact with Fcgamma receptors, which we propose is due to the binding mode of 3H5 and constitutes the primary mechanism of how ADE is avoided. | |||
Characterization of a potent and highly unusual minimally enhancing antibody directed against dengue virus.,Renner M, Flanagan A, Dejnirattisai W, Puttikhunt C, Kasinrerk W, Supasa P, Wongwiwat W, Chawansuntati K, Duangchinda T, Cowper A, Midgley CM, Malasit P, Huiskonen JT, Mongkolsapaya J, Screaton GR, Grimes JM Nat Immunol. 2018 Nov;19(11):1248-1256. doi: 10.1038/s41590-018-0227-7. Epub 2018, Oct 15. PMID:30323338<ref>PMID:30323338</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6fla" style="background-color:#fffaf0;"></div> | ||
[[Category: Flanagan | |||
[[Category: Renner | ==See Also== | ||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Dengue virus 2]] | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Flanagan A]] | |||
[[Category: Grimes JM]] | |||
[[Category: Renner M]] | |||
Latest revision as of 12:55, 23 October 2024
3H5 Fab bound to EDIII of DenV 2 Xtal form 13H5 Fab bound to EDIII of DenV 2 Xtal form 1
Structural highlights
FunctionPublication Abstract from PubMedDengue virus is a major pathogen, and severe infections can lead to life-threatening dengue hemorrhagic fever. Dengue virus exists as four serotypes, and dengue hemorrhagic fever is often associated with secondary heterologous infections. Antibody-dependent enhancement (ADE) may drive higher viral loads in these secondary infections and is purported to result from antibodies that recognize dengue virus but fail to fully neutralize it. Here we characterize two antibodies, 2C8 and 3H5, that bind to the envelope protein. Antibody 3H5 is highly unusual as it not only is potently neutralizing but also promotes little if any ADE, whereas antibody 2C8 has strong capacity to promote ADE. We show that 3H5 shows resilient binding in endosomal pH conditions and neutralizes at low occupancy. Immunocomplexes of 3H5 and dengue virus do not efficiently interact with Fcgamma receptors, which we propose is due to the binding mode of 3H5 and constitutes the primary mechanism of how ADE is avoided. Characterization of a potent and highly unusual minimally enhancing antibody directed against dengue virus.,Renner M, Flanagan A, Dejnirattisai W, Puttikhunt C, Kasinrerk W, Supasa P, Wongwiwat W, Chawansuntati K, Duangchinda T, Cowper A, Midgley CM, Malasit P, Huiskonen JT, Mongkolsapaya J, Screaton GR, Grimes JM Nat Immunol. 2018 Nov;19(11):1248-1256. doi: 10.1038/s41590-018-0227-7. Epub 2018, Oct 15. PMID:30323338[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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