📄 Elastase-mediated activation of the severe acute respiratory syndrome coronavirus spike protein at discrete sites within the S2 domain

Proteolytic priming is a common method of controlling the activation of membrane fusion mediated by viral glycoproteins. The severe acute respiratory syndrome coronavirus spike protein (SARS-CoV S) can be primed by a variety of host cell proteases, with proteolytic cleavage occurring both as the S1/S2 boundary and adjacent to a fusion peptide in the S2 domain. Here, we studied the priming of SARS-CoV S by elastase and show an important role for residue Thr795 in the S2 domain. A series of alanine mutants were generated in the vicinity of the S2 cleavage site, with the goal of examining elastase-mediated cleavage within S2. Both proteolytic cleavage and fusion activation were modulated by altering the cleavage site position. We propose a novel mechanism whereby SARS-CoV fusion protein function can be controlled by spatial regulation of the proteolytic priming site, with important implications for viral pathogenesis. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

keywords 🔗 severe acute (1373) 🔗 syndrome coronavirus (1074) 🔗 spike protein (353) 🔗 cleavage site (85) 🔗 host cell (262) 🔗 important role (140) 🔗 respiratory syndrome (2004) 🔗 acute respiratory (1734) 🔗 membrane fusion (105)

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