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D614G mutation alters SARS-CoV-2 spike conformational dynamics and protease cleavage susceptibility at the S1/S2 junction
Sophie Gobeil; Katarzyna Janowska; Shana McDowell; Katayoun Mansouri; Robert Parks; Kartik Manne; Victoria Stalls; Megan Kopp; Rory Henderson; Robert J Edwards; Barton F Haynes; Priyamvada Acharya.
Afiliação
  • Sophie Gobeil; Duke University
  • Katarzyna Janowska; Duke University
  • Shana McDowell; Duke University
  • Katayoun Mansouri; Duke University
  • Robert Parks; Duke University
  • Kartik Manne; Duke University
  • Victoria Stalls; Duke University
  • Megan Kopp; Duke University
  • Rory Henderson; Duke University
  • Robert J Edwards; Duke University
  • Barton F Haynes; Duke University
  • Priyamvada Acharya; Duke University
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-335299
ABSTRACT
The SARS-CoV-2 spike (S) protein is the target of vaccine design efforts to end the COVID-19 pandemic. Despite a low mutation rate, isolates with the D614G substitution in the S protein appeared early during the pandemic, and are now the dominant form worldwide. Here, we analyze the D614G mutation in the context of a soluble S ectodomain construct. Cryo-EM structures, antigenicity and proteolysis experiments suggest altered conformational dynamics resulting in enhanced furin cleavage efficiency of the G614 variant. Furthermore, furin cleavage altered the conformational dynamics of the Receptor Binding Domains (RBD) in the G614 S ectodomain, demonstrating an allosteric effect on the RBD dynamics triggered by changes in the SD2 region, that harbors residue 614 and the furin cleavage site. Our results elucidate SARS-CoV-2 spike conformational dynamics and allostery, and have implications for vaccine design. HighlightsO_LISARS-CoV-2 S ectodomains with or without the K986P, V987P mutations have similar structures, antigenicity and stability. C_LIO_LIThe D614G mutation alters S protein conformational dynamics. C_LIO_LID614G enhances protease cleavage susceptibility at the S protein furin cleavage site. C_LIO_LICryo-EM structures reveal allosteric effect of changes at the S1/S2 junction on RBD dynamics. C_LI
Licença
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Texto completo: Disponível Coleções: Preprints Base de dados: bioRxiv Idioma: Inglês Ano de publicação: 2020 Tipo de documento: Preprint
Texto completo: Disponível Coleções: Preprints Base de dados: bioRxiv Idioma: Inglês Ano de publicação: 2020 Tipo de documento: Preprint
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