Phosphatidylethanolamine critically supports internalization of cell-penetrating protein C inhibitor. Academic Article uri icon

Overview

abstract

  • Although their contribution remains unclear, lipids may facilitate noncanonical routes of protein internalization into cells such as those used by cell-penetrating proteins. We show that protein C inhibitor (PCI), a serine protease inhibitor (serpin), rapidly transverses the plasma membrane, which persists at low temperatures and enables its nuclear targeting in vitro and in vivo. Cell membrane translocation of PCI necessarily requires phosphatidylethanolamine (PE). In parallel, PCI acts as a lipid transferase for PE. The internalized serpin promotes phagocytosis of bacteria, thus suggesting a function in host defense. Membrane insertion of PCI depends on the conical shape of PE and is associated with the formation of restricted aqueous compartments within the membrane. Gain- and loss-of-function mutations indicate that the transmembrane passage of PCI requires a branched cavity between its helices H and D, which, according to docking studies, precisely accommodates PE. Our findings show that its specific shape enables cell surface PE to drive plasma membrane translocation of cell-penetrating PCI.

publication date

  • November 19, 2007

Research

keywords

  • Phosphatidylethanolamines
  • Protein C Inhibitor

Identity

PubMed Central ID

  • PMC2080921

Scopus Document Identifier

  • 36348944662

Digital Object Identifier (DOI)

  • 10.1083/jcb.200707165

PubMed ID

  • 18025309

Additional Document Info

volume

  • 179

issue

  • 4