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Publication Abstract from PubMed

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 A 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 alpha 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.

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 Sci Adv. 2022 Jun 17;8(24):eabp9151. doi: 10.1126/sciadv.abp9151. Epub 2022 Jun , 17. PMID:35714192^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.