7U9G

Rabies virus glycoprotein pre-fusion trimer in complex with neutralizing antibody RVA122

Summary for 7U9G

• Entry DOI: 10.2210/pdb7u9g/pdb
• EMDB information: 26397
• Descriptor: Glycoprotein, RVA122 Fab Light Chain, RVA122 Fab Heavy Chain, ... (4 entities in total)
• Functional Keywords: rabies virus glycoprotein, antibodies, viral fusion protein, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Rabies virus; More
• Total number of polymer chains: 9
• Total formula weight: 304749.29

Authors

Callaway, H.M.,Zyla, D.,Larrous, F.,Dias de Melo, G.,Hastie, K.M.,Avalos, R.D.,Agarwal, A.,Bouhry, H.,Corti, D.,Saphire, E.O. (deposition date: 2022-03-10, release date: 2022-07-20, Last modification date: 2024-10-16)

Primary citation

Callaway, H.M.,Zyla, D.,Larrous, F.,de Melo, G.D.,Hastie, K.M.,Avalos, R.D.,Agarwal, A.,Corti, D.,Bourhy, H.,Saphire, E.O.
Structure of the rabies virus glycoprotein trimer bound to a prefusion-specific neutralizing antibody.
Sci Adv, 8:eabp9151-eabp9151, 2022

PubMed Abstract: Rabies infection is nearly 100% lethal if untreated and kills more than 50,000 people annually, many of them children. Existing rabies vaccines target the rabies virus glycoprotein (RABV-G) but generate short-lived immune responses, likely because the protein is heterogeneous under physiological conditions. Here, we report the 3.39 Å cryo-electron microscopy structure of trimeric, prefusion RABV-G complexed with RVA122, a potently neutralizing human antibody. RVA122 binds to a quaternary epitope at the top of RABV-G, bridging domains and stabilizing RABV-G protomers in a prefusion state. RABV-G trimerization involves side-to-side interactions between the central α helix and adjacent loops, rather than contacts between central helices, and interactions among the fusion loops at the glycoprotein base. These results provide a basis from which to develop improved rabies vaccines based on RABV-G stabilized in the prefusion conformation.

PubMed: 35714192
DOI: 10.1126/sciadv.abp9151

Experimental method

ELECTRON MICROSCOPY (3.39 Å)