8A1E

Rabies virus glycoprotein in complex with Fab fragments of 17C7 and 1112-1 neutralizing antibodies

Summary for 8A1E

• Entry DOI: 10.2210/pdb8a1e/pdb
• EMDB information: 15073
• Descriptor: Glycoprotein, Fab 17C7 heavy chain variable domain, Fab 17C7 light chain variable domain, ... (5 entities in total)
• Functional Keywords: viral glycoprotein, antibody, complex, viral protein
• Biological source: Rabies virus strain Pasteur vaccin; More
• Total number of polymer chains: 5
• Total formula weight: 106571.37

Authors

Ng, W.M.,Fedosyuk, S.,English, S.,Augusto, G.,Berg, A.,Thorley, L.,Haselon, A.S.,Segireddy, R.R.,Bowden, T.A.,Douglas, A.D. (deposition date: 2022-06-01, release date: 2022-08-17, Last modification date: 2024-11-06)

Primary citation

Ng, W.M.,Fedosyuk, S.,English, S.,Augusto, G.,Berg, A.,Thorley, L.,Haselon, A.S.,Segireddy, R.R.,Bowden, T.A.,Douglas, A.D.
Structure of trimeric pre-fusion rabies virus glycoprotein in complex with two protective antibodies.
Cell Host Microbe, 30:1219-1230.e7, 2022

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-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.

PubMed: 35985336
DOI: 10.1016/j.chom.2022.07.014

Experimental method

ELECTRON MICROSCOPY (2.83 Å)