tetano
Editor, Senior Moderator
Sci Rep
. 2020 Oct 9;10(1):16944.
doi: 10.1038/s41598-020-74101-0.
The sequence at Spike S1/S2 site enables cleavage by furin and phospho-regulation in SARS-CoV2 but not in SARS-CoV1 or MERS-CoV
Mihkel ?rd[SUP] 1 [/SUP], Ilona Faustova[SUP] 1 [/SUP], Mart Loog[SUP] 2 [/SUP]
Affiliations
Abstract
The Spike protein of the novel coronavirus SARS-CoV2 contains an insertion [SUP]680[/SUP]SPRRAR↓SV[SUP]687[/SUP] forming a cleavage motif RxxR for furin-like enzymes at the boundary of S1/S2 subunits. Cleavage at S1/S2 is important for efficient viral entry into target cells. The insertion is absent in other CoV-s of the same clade, including SARS-CoV1 that caused the 2003 outbreak. However, an analogous cleavage motif was present at S1/S2 of the Spike protein of the more distant Middle East Respiratory Syndrome coronavirus MERS-CoV. We show that a crucial third arginine at the left middle position, comprising a motif RRxR is required for furin recognition in vitro, while the general motif RxxR in common with MERS-CoV is not sufficient for cleavage. Further, we describe a surprising finding that the two serines at the edges of the insert SPRRAR↓SV can be efficiently phosphorylated by proline-directed and basophilic protein kinases. Both phosphorylations switch off furin's ability to cleave the site. Although phospho-regulation of secreted proteins is still poorly understood, further studies, supported by a recent report of ten in vivo phosphorylated sites in the Spike protein of SARS-CoV2, could potentially uncover important novel regulatory mechanisms for SARS-CoV2.
. 2020 Oct 9;10(1):16944.
doi: 10.1038/s41598-020-74101-0.
The sequence at Spike S1/S2 site enables cleavage by furin and phospho-regulation in SARS-CoV2 but not in SARS-CoV1 or MERS-CoV
Mihkel ?rd[SUP] 1 [/SUP], Ilona Faustova[SUP] 1 [/SUP], Mart Loog[SUP] 2 [/SUP]
Affiliations
- PMID: 33037310
- DOI: 10.1038/s41598-020-74101-0
Abstract
The Spike protein of the novel coronavirus SARS-CoV2 contains an insertion [SUP]680[/SUP]SPRRAR↓SV[SUP]687[/SUP] forming a cleavage motif RxxR for furin-like enzymes at the boundary of S1/S2 subunits. Cleavage at S1/S2 is important for efficient viral entry into target cells. The insertion is absent in other CoV-s of the same clade, including SARS-CoV1 that caused the 2003 outbreak. However, an analogous cleavage motif was present at S1/S2 of the Spike protein of the more distant Middle East Respiratory Syndrome coronavirus MERS-CoV. We show that a crucial third arginine at the left middle position, comprising a motif RRxR is required for furin recognition in vitro, while the general motif RxxR in common with MERS-CoV is not sufficient for cleavage. Further, we describe a surprising finding that the two serines at the edges of the insert SPRRAR↓SV can be efficiently phosphorylated by proline-directed and basophilic protein kinases. Both phosphorylations switch off furin's ability to cleave the site. Although phospho-regulation of secreted proteins is still poorly understood, further studies, supported by a recent report of ten in vivo phosphorylated sites in the Spike protein of SARS-CoV2, could potentially uncover important novel regulatory mechanisms for SARS-CoV2.