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Structures of Ebola Virus GP and sGP in Complex with Therapeutic Antibodies
- Source :
- Nature microbiology
- Publication Year :
- 2016
-
Abstract
- The Ebola virus (EBOV) GP gene encodes two glycoproteins. The major product is a soluble, dimeric glycoprotein (sGP) that is secreted abundantly. Despite the abundance of sGP during infection, little is known regarding its structure or functional role. A minor product, resulting from transcriptional editing, is the transmembrane-anchored, trimeric viral surface glycoprotein (GP). GP mediates attachment to and entry into host cells, and is the intended target of antibody therapeutics. Because large portions of sequence are shared between GP and sGP, it has been hypothesized that sGP may potentially subvert the immune response or may contribute to pathogenicity. In this study, we present cryo-electron microscopy structures of GP and sGP in complex with GP-specific and GP/sGP cross-reactive antibodies undergoing human clinical trials. The structure of the sGP dimer presented here, in complex with both an sGP-specific antibody and a GP/sGP cross-reactive antibody, permits us to unambiguously assign the oligomeric arrangement of sGP and compare its structure and epitope presentation to those of GP. We also provide biophysical evaluation of naturally occurring GP/sGP mutations that fall within the footprints identified by our high-resolution structures. Taken together, our data provide a detailed and more complete picture of the accessible Ebolavirus glycoprotein landscape and a structural basis to evaluate patient and vaccine antibody responses towards differently structured products of the GP gene.
- Subjects :
- 0301 basic medicine
Microbiology (medical)
Immunology
Cross Reactions
medicine.disease_cause
Applied Microbiology and Biotechnology
Microbiology
Epitope
Article
03 medical and health sciences
Epitopes
Viral Proteins
0302 clinical medicine
VP40
Genetics
medicine
Humans
Amino Acid Sequence
Peptide sequence
Glycoproteins
Ebolavirus
chemistry.chemical_classification
Ebola virus
Membrane Glycoproteins
biology
Cryoelectron Microscopy
Antibodies, Monoclonal
Cell Biology
Hemorrhagic Fever, Ebola
Entry into host
Virology
3. Good health
Models, Structural
030104 developmental biology
chemistry
Antibody Formation
Mutation
biology.protein
Antibody
Protein Multimerization
Glycoprotein
Sequence Alignment
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 20585276
- Volume :
- 1
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Nature microbiology
- Accession number :
- edsair.doi.dedup.....0478433be7106e84e3d1841f955e2d78