Competitive inhibition of the endoplasmic reticulum signal peptidase by non-cleavable mutant preprotein cargos

Abstract

Background: Signal peptidase (SPase) excises the signal peptide of secretory preproteins. Results: A variant preproinsulin with a proline following the signal peptide cleavage site binds to and inhibits SPase. Conclusion: Inhibition of SPase impairs, in trans, the intracellular processing, trafficking, and maturation of secretory proteins and viral polypeptides. Significance: Our findings suggest eukaryotic SPase as a potential antiviral target.