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TitleStructure of the rabies virus glycoprotein trimer bound to a prefusion-specific neutralizing antibody.
Journal, issue, pagesSci Adv, Vol. 8, Issue 24, Page eabp9151, Year 2022
Publish dateJun 17, 2022
AuthorsHeather 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 AbstractRabies 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 linksSci Adv / PubMed:35714192 / PubMed Central
MethodsEM (single particle)
Resolution3.39 - 7.05 Å
Structure data

26397

7u9g

EMDB-26397, PDB-7u9g:
Rabies virus glycoprotein pre-fusion trimer in complex with neutralizing antibody RVA122
Method: EM (single particle) / Resolution: 3.39 Å

EMDB-26398: Rabies virus glycoprotein trimer
Method: EM (single particle) / Resolution: 6.92 Å

EMDB-26399: Rabies virus glycoprotein pre-fusion trimer in complex with neutralizing antibody RVA122, with 2 interacting fusion loops
Method: EM (single particle) / Resolution: 5.71 Å

EMDB-26400: Rabies virus glycoprotein pre-fusion trimer in complex with neutralizing antibody RVA122, with 3 bound fusion loops
Method: EM (single particle) / Resolution: 7.05 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • rabies virus
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / Rabies virus glycoprotein / antibodies / viral fusion protein / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex

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