PlumX Metrics
Embed PlumX Metrics

Role of Spike Protein Endodomains in Regulating Coronavirus Entry *

Journal of Biological Chemistry, ISSN: 0021-9258, Vol: 284, Issue: 47, Page: 32725-32734
2009
  • 57
    Citations
  • 0
    Usage
  • 75
    Captures
  • 0
    Mentions
  • 18
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    57
  • Captures
    75
  • Social Media
    18
    • Shares, Likes & Comments
      18
      • Facebook
        18

Article Description

Enveloped viruses enter cells by viral glycoprotein-mediated binding to host cells and subsequent fusion of virus and host cell membranes. For the coronaviruses, viral spike (S) proteins execute these cell entry functions. The S proteins are set apart from other viral and cellular membrane fusion proteins by their extensively palmitoylated membrane-associated tails. Palmitate adducts are generally required for protein-mediated fusions, but their precise roles in the process are unclear. To obtain additional insights into the S-mediated membrane fusion process, we focused on these acylated carboxyl-terminal intravirion tails. Substituting alanines for the cysteines that are subject to palmitoylation had effects on both S incorporation into virions and S-mediated membrane fusions. In specifically dissecting the effects of endodomain mutations on the fusion process, we used antiviral heptad repeat peptides that bind only to folding intermediates in the S-mediated fusion process and found that mutants lacking three palmitoylated cysteines remained in transitional folding states nearly 10 times longer than native S proteins. This slower refolding was also reflected in the paucity of postfusion six-helix bundle configurations among the mutant S proteins. Viruses with fewer palmitoylated S protein cysteines entered cells slowly and had reduced specific infectivities. These findings indicate that lipid adducts anchoring S proteins into virus membranes are necessary for the rapid, productive S protein refolding events that culminate in membrane fusions. These studies reveal a previously unappreciated role for covalently attached lipids on the endodomains of viral proteins eliciting membrane fusion reactions.

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know