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-Structure paper
Title | Structure of the rabies virus glycoprotein trimer bound to a prefusion-specific neutralizing antibody. |
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Journal, issue, pages | Sci Adv, Vol. 8, Issue 24, Page eabp9151, Year 2022 |
Publish date | Jun 17, 2022 |
Authors | Heather M Callaway / Dawid Zyla / Florence Larrous / Guilherme Dias de Melo / Kathryn M Hastie / Ruben Diaz Avalos / Alyssa Agarwal / Davide Corti / Hervé Bourhy / Erica Ollmann Saphire / |
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 ...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. |
External links | Sci Adv / PubMed:35714192 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.39 - 7.05 Å |
Structure data | EMDB-26397, PDB-7u9g: EMDB-26398: Rabies virus glycoprotein trimer EMDB-26399: Rabies virus glycoprotein pre-fusion trimer in complex with neutralizing antibody RVA122, with 2 interacting fusion loops EMDB-26400: Rabies virus glycoprotein pre-fusion trimer in complex with neutralizing antibody RVA122, with 3 bound fusion loops |
Chemicals | ChemComp-NAG: |
Source |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / Rabies virus glycoprotein / antibodies / viral fusion protein / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex |