Structural Analysis of Rabies Virus Glycoprotein Reveals pH-Dependent Conformational Changes and Interactions with a Neutralizing Antibody.

Abstract:

: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 ∼pH-8.0 and in the complex form with a neutralizing antibody 523-11 at ∼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.

journal_name

Cell Host Microbe

journal_title

Cell host & microbe

authors

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

doi

10.1016/j.chom.2019.12.012

subject

Has Abstract

pub_date

2020-03-11 00:00:00

pages

441-453.e7

issue

3

eissn

1931-3128

issn

1934-6069

pii

S1931-3128(19)30641-9

journal_volume

27

pub_type

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