Different residues in the SARS-CoV spike protein determine cleavage and activation by the host cell protease TMPRSS2.
2017 | Zeitschriftenartikel. Eine Publikation mit Affiliation zur Georg-August-Universität Göttingen.
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Zitiervorschlag
Different residues in the SARS-CoV spike protein determine cleavage and activation by the host cell protease TMPRSS2.
Reinke, L. M.; Spiegel, M.; Plegge, T.; Hartleib, A.; Nehlmeier, I.; Gierer, S. & Hoffmann, M. u.a. (2017)
PloS one, 12(6) art. e0179177. DOI: https://doi.org/10.1371/journal.pone.0179177
Dokumente & Medien
Details
- Autor(en)
- Reinke, Lennart Michel; Spiegel, Martin; Plegge, Teresa; Hartleib, Anika; Nehlmeier, Inga; Gierer, Stefanie; Hoffmann, Markus; Hofmann-Winkler, Heike; Winkler, Michael; Pöhlmann, Stefan
- Zusammenfassung
- The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) mediates viral entry into target cells. Cleavage and activation of SARS S by a host cell protease is essential for infectious viral entry and the responsible enzymes are potential targets for antiviral intervention. The type II transmembrane serine protease TMPRSS2 cleaves and activates SARS S in cell culture and potentially also in the infected host. Here, we investigated which determinants in SARS S control cleavage and activation by TMPRSS2. We found that SARS S residue R667, a previously identified trypsin cleavage site, is also required for S protein cleavage by TMPRSS2. The cleavage fragments produced by trypsin and TMPRSS2 differed in their decoration with N-glycans, suggesting that these proteases cleave different SARS S glycoforms. Although R667 was required for SARS S cleavage by TMPRSS2, this residue was dispensable for TMPRSS2-mediated S protein activation. Conversely, residue R797, previously reported to be required for SARS S activation by trypsin, was dispensable for S protein cleavage but required for S protein activation by TMPRSS2. Collectively, these results show that different residues in SARS S control cleavage and activation by TMPRSS2, suggesting that these processes are more complex than initially appreciated.
- Erscheinungsdatum
- 2017
- Zeitschrift
- PloS one
- ISSN
- 1932-6203
- Sprache
- Englisch