View source for 6ea5


==Structure of BDBV GPcl in complex with the pan-ebolavirus mAb ADI-15878==
<StructureSection load='6ea5' size='340' side='right'caption='[[6ea5]], [[Resolution|resolution]] 4.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ea5]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Bundibugyo_ebolavirus Bundibugyo ebolavirus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EA5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EA5 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]] 4.75&#8491;</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=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=6ea5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ea5 OCA], [https://pdbe.org/6ea5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ea5 RCSB], [https://www.ebi.ac.uk/pdbsum/6ea5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ea5 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/B8XCN0_9MONO B8XCN0_9MONO] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Only one naturally occurring human antibody has been described thus far that is capable of potently neutralizing all five ebolaviruses. Here we present two crystal structures of this rare, pan-ebolavirus neutralizing human antibody in complex with Ebola virus and Bundibugyo virus glycoproteins (GPs), respectively. The structures delineate the key protein and glycan contacts for binding that are conserved across the ebolaviruses, explain the antibody's unique broad specificity and neutralization activity, and reveal the likely mechanism behind a known escape mutation in the fusion loop region of GP2. We found that the epitope of this antibody, ADI-15878, extends along the hydrophobic paddle of the fusion loop and then dips down into a highly conserved pocket beneath the N-terminal tail of GP2, a mode of recognition unlike any other antibody elicited against Ebola virus, and likely critical for its broad activity. The fold of Bundibugyo virus glycoprotein, not previously visualized, is similar to the fold of Ebola virus GP, and ADI-15878 binds to each virus's GP with a similar strategy and angle of attack. These findings will be useful in deployment of this antibody as a broad-spectrum therapeutic and in the design of immunogens that elicit the desired broadly neutralizing immune response against all members of the ebolavirus genus and filovirus family.IMPORTANCE There are five different members of the Ebolavirus genus. Provision of vaccines and treatments able to protect against any of the five ebolaviruses is an important goal of public health. Antibodies are a desired result of vaccines and can be delivered directly as therapeutics. Most antibodies, however, are effective against only one or two, not all, of these pathogens. Only one human antibody has been thus far described to neutralize all five ebolaviruses, antibody ADI-15878. Here we describe the molecular structure of ADI-15878 bound to the relevant target proteins of Ebola virus and Bundibugyo virus. We explain how it achieves its rare breadth of activity and propose strategies to design improved vaccines capable of eliciting more antibodies like ADI-15878.

Structural Basis of Pan-Ebolavirus Neutralization by a Human Antibody against a Conserved, yet Cryptic Epitope.,West BR, Moyer CL, King LB, Fusco ML, Milligan JC, Hui S, Saphire EO MBio. 2018 Sep 11;9(5). pii: mBio.01674-18. doi: 10.1128/mBio.01674-18. PMID:30206174<ref>PMID:30206174</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ea5" style="background-color:#fffaf0;"></div>

==See Also==
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bundibugyo ebolavirus]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Fusco ML]]
[[Category: Hui S]]
[[Category: King LB]]
[[Category: Milligan JC]]
[[Category: Moyer CL]]
[[Category: Saphire EO]]
[[Category: West BR]]