+Search query
-Structure paper
Title | Structure of trimeric pre-fusion rabies virus glycoprotein in complex with two protective antibodies. |
---|---|
Journal, issue, pages | Cell Host Microbe, Vol. 30, Issue 9, Page 1219-11230.e7, Year 2022 |
Publish date | Aug 11, 2022 |
Authors | Weng M Ng / Sofiya Fedosyuk / Solomon English / Gilles Augusto / Adam Berg / Luke Thorley / Anna-Sophie Haselon / Rameswara R Segireddy / Thomas A Bowden / Alexander D Douglas / |
PubMed Abstract | Rabies virus (RABV) causes lethal encephalitis and is responsible for approximately 60,000 deaths per year. As the sole virion-surface protein, the rabies virus glycoprotein (RABV-G) mediates host- ...Rabies virus (RABV) causes lethal encephalitis and is responsible for approximately 60,000 deaths per year. As the sole virion-surface protein, the rabies virus glycoprotein (RABV-G) mediates host-cell entry. RABV-G's pre-fusion trimeric conformation displays epitopes bound by protective neutralizing antibodies that can be induced by vaccination or passively administered for post-exposure prophylaxis. We report a 2.8-Å structure of a RABV-G trimer in the pre-fusion conformation, in complex with two neutralizing and protective monoclonal antibodies, 17C7 and 1112-1, that recognize distinct epitopes. One of these antibodies is a licensed prophylactic (17C7, Rabishield), which we show locks the protein in pre-fusion conformation. Targeted mutations can similarly stabilize RABV-G in the pre-fusion conformation, a key step toward structure-guided vaccine design. These data reveal the higher-order architecture of a key therapeutic target and the structural basis of neutralization by antibodies binding two key antigenic sites, and this will facilitate the development of improved vaccines and prophylactic antibodies. |
External links | Cell Host Microbe / PubMed:35985336 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.83 Å |
Structure data | EMDB-15073, PDB-8a1e: |
Source |
|
Keywords | VIRAL PROTEIN / Viral Glycoprotein / Antibody / Complex |