EMD-26399
Rabies virus glycoprotein pre-fusion trimer in complex with neutralizing antibody RVA122, with 2 interacting fusion loops
EMD-26399
Single-particle5.71 Å
Deposition: 10/03/2022Map released: 20/07/2022
Last modified: 17/01/2024
Sample Organism:
Homo sapiens,
Rabies virus
Sample: Rabies virus glycoprotein pre-fusion trimer in complex with neutralizing antibody RVA122
Deposition Authors: Callaway HM
,
Zyla D ,
Larrous F ,
Dias de Melo G ,
Hastie KM ,
Avalos RD ,
Agarwal A ,
Bouhry H ,
Corti D ,
Saphire EO
Sample: Rabies virus glycoprotein pre-fusion trimer in complex with neutralizing antibody RVA122
Deposition Authors: Callaway HM
,
Zyla D ,
Larrous F ,
Dias de Melo G ,
Hastie KM ,
Avalos RD ,
Agarwal A ,
Bouhry H ,
Corti D ,
Saphire EO
Structure of the rabies virus glycoprotein trimer bound to a prefusion-specific neutralizing antibody.
Callaway HM ,
Zyla D ,
Larrous F ,
de Melo GD ,
Hastie KM ,
Avalos RD ,
Agarwal A ,
Corti D ,
Bourhy H ,
Saphire EO
(2022) Sci Adv , 8 , eabp9151 - eabp9151
,
Zyla D ,
Larrous F ,
de Melo GD ,
Hastie KM ,
Avalos RD ,
Agarwal A ,
Corti D ,
Bourhy H ,
Saphire EO
(2022) Sci Adv , 8 , eabp9151 - eabp9151
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.
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.