Proton-coupled protein transport through the anthrax toxin channel

Alan Finkelstein

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Anthrax toxin consists of three proteins (approx. 90 kDa each): lethal factor (LF); oedema factor (OF); and protective antigen (PA). The former two are enzymes that act when they reach the cytosol of a targeted cell. To enter the cytosol, however, which they do after being endocytosed into an acidic vesicle compartment, they require the third component, PA. PA (or rather its proteolytically generated fragment PA63) forms at low pH a heptameric β-barrel channel, (PA63)7, through which LF and OF are transported-a phenomenon we have demonstrated in planar phospholipid bilayers. It might appear that (PA63)7 simply forms a large hole through which LF and OF diffuse. However, LF and OF are folded proteins, much too large to fit through the approximately 15 Å diameter (PA63)7 β-barrel. This paper discusses how the (PA63)7 channel both participates in the unfolding of LF and OF and functions in their translocation as a proton-protein symporter.

Original languageEnglish (US)
Pages (from-to)209-215
Number of pages7
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Volume364
Issue number1514
DOIs
StatePublished - 2009

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Keywords

  • Lethal factor
  • Planar bilayer membranes
  • Protein unfolding
  • Voltage-driven transport

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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