View source for 9vts


==EBOV GP/1A10-VHH complex==
<StructureSection load='9vts' size='340' side='right'caption='[[9vts]], [[Resolution|resolution]] 2.56&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9vts]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Ebola_virus_-_Gabon_(1994-1997) Ebola virus - Gabon (1994-1997)], [https://en.wikipedia.org/wiki/Vicugna_pacos Vicugna pacos] and [https://en.wikipedia.org/wiki/Zaire_ebolavirus Zaire ebolavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9VTS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9VTS FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.56&#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=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=9vts FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9vts OCA], [https://pdbe.org/9vts PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9vts RCSB], [https://www.ebi.ac.uk/pdbsum/9vts PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9vts ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/G8DB49_9MONO G8DB49_9MONO] Acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in GP2, releasing the fusion hydrophobic peptide.[ARBA:ARBA00060272]  Functions as a decoy for anti-GP1,2 antibodies thereby contributing to viral immune evasion. Interacts and activates host macrophages and dendritic cells inducing up-regulation of cytokine transcription. This effect is mediated throught activation of host TLR4.[ARBA:ARBA00058844]
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== Publication Abstract from PubMed ==
The highly lethal Ebola virus species-Zaire (EBOV), Sudan (SUDV), and Bundibugyo (BDBV)-pose persistent threats to global health. Current antibody therapies target EBOV but lack broad neutralization across ebolaviruses. Recent pan-ebolavirus strategies rely on antibody cocktails. Here, we identified two camelid-derived nanobodies (1A10 and BA2) that neutralize EBOV, SUDV, and BDBV in vitro and protect female rodents against these pathogens. High-resolution cryo-EM structures of their GP complexes showed that 1A10 and BA2 bind conserved but non-overlapping epitopes near the GP1 base and GP2's internal fusion loop (IFL), and biochemical analyses revealed their distinct neutralization mechanisms. To further improve efficacy, we engineered a bispecific antibody (BA2-1A10) via GS linker-mediated IgG-Fc fusion, which provided highly potent protection against all three viruses in female rodents model and positions it as a strong broad-spectrum anti-ebolavirus candidate. Our work demonstrates a structure-guided bispecific nanobody strategy for pan-ebolavirus therapy and highlights compact antibodies for next-generation antivirals.

A highly potent nanobody-based bispecific therapeutic provides broad-spectrum protection against ebolavirus.,Wang M, Zhang X, Li W, Yao Y, Li E, Zhang B, Zhou J, Liu S, Gao Y, Zhu Z, Zhu L, Liu M, Hu J, Peng C, Li F, Chen M, Liu H, Yao C, Shang Y, Yan F, Gong P, Jin T, Chiu S Nat Commun. 2026 Mar 17;17(1):4040. doi: 10.1038/s41467-026-70464-6. PMID:41839884<ref>PMID:41839884</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9vts" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Vicugna pacos]]
[[Category: Zaire ebolavirus]]
[[Category: Gong P]]
[[Category: Jin T]]
[[Category: Wang M]]