Proton-coupled protein transport through the anthrax toxin channel

Alan Finkelstein

doi:10.1098/rstb.2008.0126

Proton-coupled protein transport through the anthrax toxin channel

Alan Finkelstein

Research output: Contribution to journal › Article › peer-review

22 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 language	English (US)
Pages (from-to)	209-215
Number of pages	7
Journal	Philosophical Transactions of the Royal Society B: Biological Sciences
Volume	364
Issue number	1514
DOIs	https://doi.org/10.1098/rstb.2008.0126
State	Published - 2009
Externally published	Yes

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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10.1098/rstb.2008.0126

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title = "Proton-coupled protein transport through the anthrax toxin channel",

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 {\AA} 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.",

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AU - Finkelstein, Alan

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

KW - Lethal factor

KW - Planar bilayer membranes

KW - Protein unfolding

KW - Voltage-driven transport

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JO - Philosophical Transactions of the Royal Society B: Biological Sciences

JF - Philosophical Transactions of the Royal Society B: Biological Sciences

IS - 1514

ER -

Proton-coupled protein transport through the anthrax toxin channel

Abstract

Keywords

ASJC Scopus subject areas

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