Singular Interaction between an Antimetastatic Agent and the Lipid Bilayer: The Ohmline Case

ACS Omega
Fernando E HerreraAna M Bouchet

Abstract

SK3 channels are abnormaly expressed in metastatic cells, and Ohmline (OHM), an ether lipid, has been shown to reduce the activity of SK3 channels and the migration capacity of cancer cells. OHM incorporation into the plasma membrane is proposed to dissociate the protein complex formed between SK3 and Orai1, a potassium and a calcium channel, respectively, and would lead to a modification in the lipid environment of both the proteins. Here, we report the synthesis of deuterated OHM that affords the determination, through solid-state NMR, of its entire partitioning into membranes mimicking the SK3 environment. Use of deuterated lipids affords the demonstration of an OHM-induced membrane disordering, which is dose-dependent and increases with increasing amounts of cholesterol (CHOL). Molecular dynamics simulations comfort the disordering action and show that OHM interacts with the carbonyl and phosphate groups of stearoylphosphatidylcholine and sphingomyelin and to a minor extent with CHOL. OHM is thus proposed to remove the CHOL OH moieties away from their main binding sites, forcing a new rearrangement with other lipid groups. Such an interaction takes its origin at the lipid-water interface, but it propagates toward the entire...Continue Reading

References

Aug 1, 1977·Quarterly Reviews of Biophysics·J Seelig
Aug 10, 1992·Biochimica Et Biophysica Acta·L V SchaginaK Blastó
Mar 21, 1983·Biochimica Et Biophysica Acta·J H Davis
Mar 26, 1996·Biochemistry·J A LundbaekO S Andersen
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Sep 9, 1997·Biochemistry·G GimplF Fahrenholz
Apr 1, 2000·The Journal of Biological Chemistry·F MaingretE Honoré
Nov 7, 2000·Biochimica Et Biophysica Acta·J F Nagle, S Tristram-Nagle
Feb 4, 2003·Journal of Lipid Research·Linda J Pike
Sep 2, 2003·Biochimica Et Biophysica Acta·Nanna K JorgensenSøren-Peter Olesen
Aug 10, 2004·Biophysical Journal·Sagar A PanditH L Scott
Oct 15, 2005·Proceedings of the National Academy of Sciences of the United States of America·Seok-Yong LeeRoderick MacKinnon
Nov 24, 2006·Molecular Cancer Therapeutics·Marie PotierChristophe Vandier
Dec 1, 2006·Nature·Daniel SchmidtRoderick MacKinnon
Feb 22, 2007·The Journal of Nutrition·Philip C Calder, Parveen Yaqoob
Mar 21, 2007·Methods : a Companion to Methods in Enzymology·Christian KandtD Peter Tieleman
Dec 15, 2007·The Journal of Biological Chemistry·Abderrahmane AliouaEnrico Stefani
May 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Yulia EpshteinIrena Levitan
Jun 2, 2009·Biochemical and Biophysical Research Communications·Vivek GargKeli Hu
Jul 2, 2009·Journal of Chemical Biology·Erick J Dufourc
Aug 4, 2009·Experimental Cell Research·Aurelie ChantomeVirginie Joulin
Sep 8, 2009·Biochimica Et Biophysica Acta·Jacques Fantini, Francisco J Barrantes
Sep 11, 2009·The Journal of Biological Chemistry·Dev K SinghIrena Levitan
Oct 20, 2010·British Journal of Pharmacology·M PotierC Vandier
Dec 30, 2011·Current Medicinal Chemistry·A GiraultC Vandier
Jan 14, 2012·The Journal of Chemical Physics·Fernando E Herrera, Sergio Pantano
May 30, 2013·Organic & Biomolecular Chemistry·Charlotte M SevrainPaul-Alain Jaffrès
Jun 19, 2013·Cancer Research·Aurélie ChantômeChristophe Vandier
Feb 5, 2014·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Carl D Bortner, John A Cidlowski
Feb 20, 2014·Proceedings of the National Academy of Sciences of the United States of America·Stephen G BrohawnRoderick MacKinnon
Jun 13, 2014·Science Translational Medicine·Jamey P WeichertJohn S Kuo
Jul 23, 2014·The Journal of Cell Biology·Xi Huang, Lily Yeh Jan
Sep 18, 2014·Journal of the American Chemical Society·Helgi I IngólfssonSiewert J Marrink
Dec 30, 2014·Biochimica Et Biophysica Acta·Elena LastraioliAnnarosa Arcangeli
Mar 31, 2015·Langmuir : the ACS Journal of Surfaces and Colloids·Matheus Malta de SáDaniel Blankschtein
Mar 1, 2008·Journal of Chemical Theory and Computation·Berk HessErik Lindahl
Dec 15, 2015·Biochimica Et Biophysica Acta·Sara CapponiStephen H White
Jun 10, 2016·ChemMedChem·Wilfried BerthePaul-Alain Jaffrès
Jun 12, 2016·Pharmacology & Therapeutics·Paul-Alain JaffrèsChristophe Vandier

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Citations

Oct 14, 2020·European Journal of Medicinal Chemistry·Alicia BauduinPaul-Alain Jaffrès
Mar 10, 2021·Organic & Biomolecular Chemistry·Charlotte M SevrainPaul-Alain Jaffrès
Feb 26, 2021·Scientific Reports·Ana Marta de MatosAmélia P Rauter
Jun 15, 2019·Cell Calcium·Sana KoubaMarie Potier-Cartereau

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Methods Mentioned

BETA
NMR

Software Mentioned

Gromacs package
Gromacs

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