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[[ | ==Crystal structure of Sudan Ebolavirus Glycoprotein (strain Boniface) bound to 16F6== | ||
<StructureSection load='3ve0' size='340' side='right' caption='[[3ve0]], [[Resolution|resolution]] 3.35Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3ve0]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [http://en.wikipedia.org/wiki/Sudan_ebolavirus Sudan ebolavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VE0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VE0 FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3s88|3s88]], [[3csy|3csy]]</td></tr> | |||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=186540 Sudan ebolavirus])</td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ve0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ve0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ve0 RCSB], [http://www.ebi.ac.uk/pdbsum/3ve0 PDBsum]</span></td></tr> | |||
<table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
There are five antigenically distinct ebolaviruses that cause hemorrhagic fever in humans or non-human primates (Ebola virus, Sudan virus, Reston virus, Tai Forest virus, and Bundibugyo virus). The small handful of antibodies known to neutralize the ebolaviruses bind to the surface glycoprotein termed GP(1,2). Curiously, some antibodies against them are known to neutralize in vitro but not protect in vivo, whereas other antibodies are known to protect animal models in vivo, but not neutralize in vitro. A detailed understanding of what constitutes a neutralizing and/or protective antibody response is critical for development of novel therapeutic strategies. Here, we show that paradoxically, a lower affinity antibody with restricted access to its epitope confers better neutralization than a higher affinity antibody against a similar epitope, suggesting that either subtle differences in epitope, or different characteristics of the GP(1,2) molecules themselves, confer differential neutralization susceptibility. Here, we also report the crystal structure of trimeric, prefusion GP(1,2) from the original 1976 Boniface variant of Sudan virus complexed with 16F6, the first antibody known to neutralize Sudan virus, and compare the structure to that of Sudan virus, variant Gulu. We discuss new structural details of the GP(1)-GP(2) clamp, thermal motion of various regions in GP(1,2) across the two viruses visualized, details of differential interaction of the crystallized neutralizing antibodies, and their relevance for virus neutralization. | |||
Structural basis for differential neutralization of ebolaviruses.,Bale S, Dias JM, Fusco ML, Hashiguchi T, Wong AC, Liu T, Keuhne AI, Li S, Woods VL Jr, Chandran K, Dye JM, Saphire EO Viruses. 2012 Apr;4(4):447-70. Epub 2012 Apr 5. PMID:22590681<ref>PMID:22590681</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | |||
*[[Antibody|Antibody]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
[[ | |||
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< | |||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Sudan ebolavirus]] | [[Category: Sudan ebolavirus]] | ||
Revision as of 11:25, 5 June 2014
Crystal structure of Sudan Ebolavirus Glycoprotein (strain Boniface) bound to 16F6Crystal structure of Sudan Ebolavirus Glycoprotein (strain Boniface) bound to 16F6
Structural highlights
Publication Abstract from PubMedThere are five antigenically distinct ebolaviruses that cause hemorrhagic fever in humans or non-human primates (Ebola virus, Sudan virus, Reston virus, Tai Forest virus, and Bundibugyo virus). The small handful of antibodies known to neutralize the ebolaviruses bind to the surface glycoprotein termed GP(1,2). Curiously, some antibodies against them are known to neutralize in vitro but not protect in vivo, whereas other antibodies are known to protect animal models in vivo, but not neutralize in vitro. A detailed understanding of what constitutes a neutralizing and/or protective antibody response is critical for development of novel therapeutic strategies. Here, we show that paradoxically, a lower affinity antibody with restricted access to its epitope confers better neutralization than a higher affinity antibody against a similar epitope, suggesting that either subtle differences in epitope, or different characteristics of the GP(1,2) molecules themselves, confer differential neutralization susceptibility. Here, we also report the crystal structure of trimeric, prefusion GP(1,2) from the original 1976 Boniface variant of Sudan virus complexed with 16F6, the first antibody known to neutralize Sudan virus, and compare the structure to that of Sudan virus, variant Gulu. We discuss new structural details of the GP(1)-GP(2) clamp, thermal motion of various regions in GP(1,2) across the two viruses visualized, details of differential interaction of the crystallized neutralizing antibodies, and their relevance for virus neutralization. Structural basis for differential neutralization of ebolaviruses.,Bale S, Dias JM, Fusco ML, Hashiguchi T, Wong AC, Liu T, Keuhne AI, Li S, Woods VL Jr, Chandran K, Dye JM, Saphire EO Viruses. 2012 Apr;4(4):447-70. Epub 2012 Apr 5. PMID:22590681[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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