The Spike protein of the novel coronavirus SARS-CoV2 contains an insertion 680 S PRRA R↓SV 687 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 R R xR 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 S PRRAR↓ S V 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.
【저자키워드】 Biochemistry, Molecular biology, 【초록키워드】 coronavirus, SARS-CoV2, furin, spike, arginine, in vitro, MERS-CoV, viral entry, Novel coronavirus, Regulatory, Protein, outbreak, Phosphorylation, clade, cleavage, respiratory, in vivo, mechanism, Middle East, target cells, protein kinases, Serine, enzyme, S1/S2, insertion, motif, PRRA, S1/S2 subunits, caused, required, supported, phosphorylated, the Spike, cleave, basophilic, secreted protein, 【제목키워드】 SARS-CoV2, furin, spike, MERS-CoV, cleavage, sequence, S1/S2 site,