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Publication Abstract from PubMed

Rabies virus (RABV), the etiological agent for the lethal disease of rabies, is a deadly zoonotic pathogen. The RABV glycoprotein (RABV-G) is a key factor mediating virus entry and the major target of neutralizing antibodies. Here, we report the crystal structures of RABV-G solved in the free form at approximately pH-8.0 and in the complex form with a neutralizing antibody 523-11 at approximately pH-6.5, respectively. RABV-G has three domains, and the basic-to-acidic pH change results in large domain re-orientations and concomitant domain-linker re-constructions, switching it from a bent hairpin conformation into an extended conformation. During such low-pH-induced structural transitions, residues located in the domain-linker are found to play important roles in glycoprotein-mediated membrane fusion. Finally, the antibody interacts with RABV-G mainly through its heavy chain and binds to a bipartite conformational epitope in the viral protein for neutralization. These structures provide valuable information for vaccine and drug design.

Structural Analysis of Rabies Virus Glycoprotein Reveals pH-Dependent Conformational Changes and Interactions with a Neutralizing Antibody.,Yang F, Lin S, Ye F, Yang J, Qi J, Chen Z, Lin X, Wang J, Yue D, Cheng Y, Chen Z, Chen H, You Y, Zhang Z, Yang Y, Yang M, Sun H, Li Y, Cao Y, Yang S, Wei Y, Gao GF, Lu G Cell Host Microbe. 2020 Jan 23. pii: S1931-3128(19)30641-9. doi:, 10.1016/j.chom.2019.12.012. PMID:32004500^[1]

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