Protein translocation through anthrax toxin channels formed in planar lipid bilayers

Biophysical Journal
Sen ZhangAlan Finkelstein

Abstract

The 63-kDa fragment of the protective antigen (PA) component of anthrax toxin forms a heptameric channel, (PA63)7, in acidic endosomal membranes that leads to the translocation of edema factor (EF) and lethal factor (LF) to the cytosol. It also forms a channel in planar phospholipid bilayer membranes. What role does this channel play in the translocation of EF and LF? We report that after the 263-residue N-terminal piece of LF (LFN) binds to its receptor on the (PA63)7 channel and its N-terminal end enters the channel at small positive voltages to block it, LFN is translocated through the channel to the opposite side at large positive voltages, thereby unblocking it. Thus, all of the translocation machinery is contained in the (PA63)7 channel, and translocation does not require any cellular proteins. The kinetics of this translocation are S-shaped, voltage-dependent, and occur on a timescale of seconds. We suggest that the translocation process might be explained simply by electrophoresis of unfolded LFN through the channel, but the refolding of the N-terminal half of LFN as it emerges from the channel may also provide energy for moving the rest of the molecule through the channel.

References

Mar 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·D H HochL L Simpson
Apr 1, 1994·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·M AnbariR W Van Dyke
Jan 1, 1994·The American Journal of Physiology·R W Van Dyke, J D Belcher
Feb 27, 1997·Nature·C PetosaR C Liddington
Apr 2, 1998·Biochemistry·E L BensonR J Collier
Oct 21, 1998·Trends in Microbiology·I R HendersonJ P Nataro
Jul 21, 1999·Proceedings of the National Academy of Sciences of the United States of America·K J OhA Finkelstein
Dec 13, 2000·The Journal of Biological Chemistry·B R SellmanR J Collier
Nov 7, 2001·The Journal of General Physiology·M Gordon, A Finkelstein
Nov 9, 2001·Nature·A D PanniferR C Liddington
Jan 16, 2002·Biochemistry·Jeremy MogridgeR John Collier
Jan 30, 2002·Biochemistry·Shilla NassiAlan Finkelstein
Mar 12, 2002·Nature Structural Biology·Shihai HuangAndreas Matouschek
May 9, 2002·Proceedings of the National Academy of Sciences of the United States of America·Kristina CunninghamR John Collier
May 29, 2002·The EMBO Journal·Lisa HeinsJürgen Soll
Dec 3, 2002·Nature Structural Biology·Lilia K Koriazova, Mauricio Montal
Jan 16, 2003·Biochemical Pharmacology·Kenneth A Bradley, John A T Young
Oct 7, 2003·Nature Structural Biology·Genji KurisuWilliam A Cramer
Oct 23, 2003·Annual Review of Cell and Developmental Biology·R John Collier, John A T Young
Mar 12, 2004·The EMBO Journal·Clasien J OomenPiet Gros

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Citations

Feb 16, 2006·Biochemistry·Kenneth A ChristensenR John Collier
Oct 13, 2012·Chemical Reviews·Ekaterina M Nestorovich, Sergey M Bezrukov
Oct 11, 2005·Proceedings of the National Academy of Sciences of the United States of America·Vladimir A KarginovSergey M Bezrukov
Oct 28, 2005·Proceedings of the National Academy of Sciences of the United States of America·D Borden LacyR John Collier
Jun 15, 2007·Proceedings of the National Academy of Sciences of the United States of America·Audrey Fischer, Mauricio Montal
Nov 21, 2009·Proceedings of the National Academy of Sciences of the United States of America·Katie L ThorenBryan A Krantz
Sep 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Audrey FischerR John Collier
Jan 12, 2010·The Journal of Biological Chemistry·Blythe E JanowiakR John Collier
Apr 22, 2011·The Journal of Biological Chemistry·Michael J BrownBryan A Krantz
Nov 2, 2012·The Journal of Biological Chemistry·Sarah L Wynia-SmithBryan A Krantz
Aug 30, 2008·The Journal of General Physiology·Damon S Anderson, Robert O Blaustein
Feb 11, 2009·The Journal of General Physiology·Daniel BasilioAlan Finkelstein
Mar 16, 2011·The Journal of General Physiology·Robert O Blaustein
Jun 1, 2011·The Journal of General Physiology·Daniel BasilioAlan Finkelstein
Oct 30, 2008·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Alan Finkelstein
May 9, 2007·Antimicrobial Agents and Chemotherapy·Ana M SanchezKenneth A Bradley
Jun 21, 2005·Molecular and Cellular Biology·Maen Qa'danR John Collier
Aug 2, 2007·Canadian Journal of Microbiology·G T Vilas-BôasO M N Arantes
Sep 13, 2013·Annual Review of Microbiology·Anne H Delcour
Mar 6, 2007·Annual Review of Biochemistry·John A T Young, R John Collier
Aug 21, 2013·The Journal of Chemical Physics·Brian J NabloJohn J Kasianowicz
Jun 21, 2006·Proceedings of the National Academy of Sciences of the United States of America·Roman A Melnyk, R John Collier
Jul 27, 2006·Proceedings of the National Academy of Sciences of the United States of America·John J KasianowiczVincent M Stanford
Mar 23, 2012·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Andrew W Artenstein, Steven M Opal
May 24, 2007·Molecular Membrane Biology·Sónia Troeira HenriquesMiguel A R B Castanho
Sep 12, 2006·FEBS Letters·Núria Reig, F Gisou van der Goot
Aug 26, 2014·Toxins·Philip A Gurnev, Ekaterina M Nestorovich
Jan 23, 2014·Expert Opinion on Drug Discovery·Ekaterina M Nestorovich, Sergey M Bezrukov
Jul 6, 2014·Journal of Molecular Biology·Aviva Schiffmiller, Alan Finkelstein
Dec 15, 2015·Pathogens and Disease·Sergey M Bezrukov, Ekaterina M Nestorovich
Aug 19, 2015·Biochimica Et Biophysica Acta·O KnappM R Popoff
Jun 22, 2010·Current Opinion in Biotechnology·Sheereen MajdMichael Mayer
Jul 15, 2015·The Journal of General Physiology·Aviva SchiffmillerAlan Finkelstein
Jul 1, 2009·Molecular Aspects of Medicine·R John Collier
Jul 18, 2009·Protein Science : a Publication of the Protein Society·Gregory VernierR John Collier
Jul 22, 2006·Molecular Microbiology·Francisco J Maldonado-ArochoKenneth A Bradley
Jan 24, 2009·Protein Science : a Publication of the Protein Society·Blythe E JanowiakR John Collier
Mar 30, 2011·Molecular Microbiology·Katie L Thoren, Bryan A Krantz
Mar 1, 2012·Protein Science : a Publication of the Protein Society·Geoffrey K FeldBryan A Krantz
Mar 16, 2016·Toxins·Sarah FriebeJérôme Bürgi
Feb 1, 2005·Trends in Microbiology·Laurence AbramiF Gisou van der Goot
Dec 14, 2005·Journal of Molecular Biology·Bryan A KrantzR John Collier
Jan 26, 2011·Proceedings of the National Academy of Sciences of the United States of America·Laura D Jennings-AntipovR John Collier

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