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TitleStructure of trimeric pre-fusion rabies virus glycoprotein in complex with two protective antibodies.
Journal, issue, pagesCell Host Microbe, Vol. 30, Issue 9, Page 1219-11230.e7, Year 2022
Publish dateAug 11, 2022
AuthorsWeng M Ng / Sofiya Fedosyuk / Solomon English / Gilles Augusto / Adam Berg / Luke Thorley / Anna-Sophie Haselon / Rameswara R Segireddy / Thomas A Bowden / Alexander D Douglas /
PubMed AbstractRabies virus (RABV) causes lethal encephalitis and is responsible for approximately 60,000 deaths per year. As the sole virion-surface protein, the rabies virus glycoprotein (RABV-G) mediates host- ...Rabies virus (RABV) causes lethal encephalitis and is responsible for approximately 60,000 deaths per year. As the sole virion-surface protein, the rabies virus glycoprotein (RABV-G) mediates host-cell entry. RABV-G's pre-fusion trimeric conformation displays epitopes bound by protective neutralizing antibodies that can be induced by vaccination or passively administered for post-exposure prophylaxis. We report a 2.8-Å structure of a RABV-G trimer in the pre-fusion conformation, in complex with two neutralizing and protective monoclonal antibodies, 17C7 and 1112-1, that recognize distinct epitopes. One of these antibodies is a licensed prophylactic (17C7, Rabishield), which we show locks the protein in pre-fusion conformation. Targeted mutations can similarly stabilize RABV-G in the pre-fusion conformation, a key step toward structure-guided vaccine design. These data reveal the higher-order architecture of a key therapeutic target and the structural basis of neutralization by antibodies binding two key antigenic sites, and this will facilitate the development of improved vaccines and prophylactic antibodies.
External linksCell Host Microbe / PubMed:35985336 / PubMed Central
MethodsEM (single particle)
Resolution2.83 Å
Structure data

15073

8a1e

EMDB-15073, PDB-8a1e:
Rabies virus glycoprotein in complex with Fab fragments of 17C7 and 1112-1 neutralizing antibodies
Method: EM (single particle) / Resolution: 2.83 Å

Source
  • Rabies lyssavirus
  • rabies virus strain pasteur vaccin
  • homo sapiens (human)
  • mus musculus (house mouse)
KeywordsVIRAL PROTEIN / Viral Glycoprotein / Antibody / Complex

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