Different residues in the SARS-CoV spike protein determine cleavage and activation by the host cell protease TMPRSS2
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
PloS one - 12(2017), 6 vom: 13., Seite e0179177 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Reinke, Lennart Michel [VerfasserIn] |
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| Links: |
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| Themen: |
EC 3.4.21.- |
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| Anmerkungen: |
Date Completed 06.10.2017 Date Revised 15.04.2020 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1371/journal.pone.0179177 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM273147455 |
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| 100 | 1 | |a Reinke, Lennart Michel |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Different residues in the SARS-CoV spike protein determine cleavage and activation by the host cell protease TMPRSS2 |
| 264 | 1 | |c 2017 | |
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| 500 | |a Date Completed 06.10.2017 | ||
| 500 | |a Date Revised 15.04.2020 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Spike Glycoprotein, Coronavirus |2 NLM | |
| 650 | 7 | |a spike glycoprotein, SARS-CoV |2 NLM | |
| 650 | 7 | |a Serine Endopeptidases |2 NLM | |
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| 650 | 7 | |a TMPRSS2 protein, human |2 NLM | |
| 650 | 7 | |a EC 3.4.21.- |2 NLM | |
| 700 | 1 | |a Spiegel, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Plegge, Teresa |e verfasserin |4 aut | |
| 700 | 1 | |a Hartleib, Anika |e verfasserin |4 aut | |
| 700 | 1 | |a Nehlmeier, Inga |e verfasserin |4 aut | |
| 700 | 1 | |a Gierer, Stefanie |e verfasserin |4 aut | |
| 700 | 1 | |a Hoffmann, Markus |e verfasserin |4 aut | |
| 700 | 1 | |a Hofmann-Winkler, Heike |e verfasserin |4 aut | |
| 700 | 1 | |a Winkler, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Pöhlmann, Stefan |e verfasserin |4 aut | |
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