An Effective Electric Dipole Model for Voltage-induced Gating Mechanism of Lysenin

Scientific Reports
Radwan Al FaouriGregory Salamo

Abstract

Lysenin is a pore-forming toxin, which self-inserts open channels into sphingomyelin containing membranes and is known to be voltage regulated. The mechanistic details of its voltage gating mechanism, however, remains elusive despite much recent efforts. Here, we have employed a novel combination of experimental and computational techniques to examine a model for voltage gating, that is based on the existence of an "effective electric dipole" inspired by recent reported structures of lysenin. We support this mechanism by the observations that (i) the charge-reversal and neutralization substitutions in lysenin result in changing its electrical gating properties by modifying the strength of the dipole, and (ii) an increase in the viscosity of the solvent increases the drag force and slows down the gating. In addition, our molecular dynamics (MD) simulations of membrane-embedded lysenin provide a mechanistic picture for lysenin conformational changes, which reveals, for the first time, the existence of a lipid-dependent bulge region in the pore-forming module of lysenin, which may explain the gating mechanism of lysenin at a molecular level.

References

Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
May 29, 1997·The New England Journal of Medicine·M J Ackerman, D E Clapham
Aug 23, 2001·Proceedings of the National Academy of Sciences of the United States of America·N A BakerJ A McCammon
May 2, 2003·Nature·Youxing JiangRoderick MacKinnon
May 2, 2003·Nature·Youxing JiangRoderick MacKinnon
Dec 4, 2003·Biophysical Journal·Ekaterina M NestorovichSergey M Bezrukov
Mar 30, 2004·Neuron·Yong ZhaoWilliam A Catterall
Jun 25, 2004·Nucleic Acids Research·Todd J DolinskyNathan A Baker
Jul 28, 2004·Biochemistry·Etsuko KiyokawaToshihide Kobayashi
Apr 9, 2005·IEEE Transactions on Nanobioscience·Francisco Bezanilla
Oct 14, 2005·Journal of Computational Chemistry·James C PhillipsKlaus Schulten
Jun 8, 2006·Biochemical and Biophysical Research Communications·Toru IdeToshio Yanagida
Jan 24, 2007·Toxicon : Official Journal of the International Society on Toxinology·William A CatterallTodd Scheuer
Jan 8, 2008·Biochimica Et Biophysica Acta·Monika HerećWiesław I Gruszecki
Mar 21, 2008·Nature Reviews. Molecular Cell Biology·Francisco Bezanilla
Oct 27, 2009·Biophysical Chemistry·Daniel FologeaGreg Salamo
Apr 9, 2010·The Journal of Physiology·Dimitri M Kullmann, Stephen G Waxman
May 26, 2010·The Journal of Physical Chemistry. B·Jeffery B KlaudaRichard W Pastor
Aug 21, 2010·Biophysical Chemistry·Daniel FologeaGreg J Salamo
Jun 21, 2011·PloS One·Pawel SzczesnyMarcin Grynberg
Aug 6, 2011·Analytical and Bioanalytical Chemistry·Daniel FologeaGreg J Salamo
Sep 29, 2011·Biochimica Et Biophysica Acta·Daniel FologeaGreg J Salamo
Dec 14, 2011·Proceedings of the National Academy of Sciences of the United States of America·Vladimir Yarov-YarovoyWilliam A Catterall
Sep 27, 2012·Toxins·John Gilchrist, Frank Bosmans
Nov 28, 2012·Nature Cell Biology·Karthik MallilankaramanMuniswamy Madesh
Oct 1, 2013·Biophysical Chemistry·Eric KruegerGreg Salamo
Jan 1, 2014·Structure·Kevin W HuynhVera Y Moiseenkova-Bell
Apr 7, 2016·Nature Communications·Monika Bokori-BrownChristos G Savva
May 14, 2016·Nature Communications·Marjetka PodobnikGregor Anderluh
Jan 30, 2019·ACS Central Science·Kalyan ImmadisettyMahmoud Moradi

❮ Previous
Next ❯

Citations

Jan 18, 2020·Biomolecules·Denis G KnyazevPeter Pohl

❮ Previous
Next ❯

Datasets Mentioned

BETA
D85846

Methods Mentioned

BETA
PCR

Software Mentioned

- GUI
CHARMM
Adaptive Poisson - Boltzmann Solver ( APBS )
Membrane Builder
GUI
PDB2PQR
Visual Molecular Dynamics ( VMD )
NAMD
OriginLab
Origin

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.