title: The activation mode of the mechanosensitive ion channel, MscL, by lysophosphatidylcholine differs from tension-induced gating.
abstract: One of the best-studied mechanosensitive channels is the mechanosensitive channel of large conductance (MscL). MscL senses tension in the membrane evoked by an osmotic down shock and directly couples it to large conformational changes leading to the opening of the channel. Spectroscopic techniques offer unique possibilities to monitor these conformational changes if it were possible to generate tension in the lipid bilayer, the native environment of MscL, during the measurements. To this end, asymmetric insertion of l-α-lysophosphatidylcholine (LPC) into the lipid bilayer has been effective; however, how LPC activates MscL is not fully understood. Here, the effects of LPC on tension-sensitive mutants of a bacterial MscL and on MscL homologs with different tension sensitivities are reported, leading to the conclusion that the mode of action of LPC is different from that of applied tension. Our results imply that LPC shifts the free energy of gating by interfering with MscL-membrane coupling. Furthermore, we demonstrate that the fine-tuned addition of LPC can be used for controlled activation of MscL in spectroscopic studies.
authors: Groningen Biomolecular Sciences and Biotechnology Institute, Groningen, The Netherlands;
authors: Nobina
authors: N
authors: Mukherjee
authors: Groningen Biomolecular Sciences and Biotechnology Institute, Groningen, The Netherlands;
authors: Mac Donald
authors: MD
authors: Jose
authors: Groningen Biomolecular Sciences and Biotechnology Institute, Groningen, The Netherlands; Zernike Institute for Advanced Materials, University of Groningen, Groningen, The Netherlands; and.
authors: Jan Peter
authors: JP
authors: Birkner
authors: Groningen Biomolecular Sciences and Biotechnology Institute, Groningen, The Netherlands;
authors: Martin
authors: M
authors: Walko
authors: Groningen Biomolecular Sciences and Biotechnology Institute, Groningen, The Netherlands;
authors: Helgi I
authors: HI
authors: Ingólfsson
authors: Groningen Biomolecular Sciences and Biotechnology Institute, Groningen, The Netherlands;
authors: Anna
authors: A
authors: Dimitrova
authors: Groningen Biomolecular Sciences and Biotechnology Institute, Groningen, The Netherlands;
authors: Clément
authors: C
authors: Arnarez
authors: Groningen Biomolecular Sciences and Biotechnology Institute, Groningen, The Netherlands;
authors: Siewert J
authors: SJ
authors: Marrink
authors: Groningen Biomolecular Sciences and Biotechnology Institute, Groningen, The Netherlands; Neuroscience Department, University Medical Centre Groningen, Groningen, The Netherlands a.kocer@umcg.nl.
authors: Armağan
authors: A
authors: Koçer
mesh_terms: D000595:Amino Acid Sequence; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism*; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry / Q000378:metabolism*; D008051:Lipid Bilayers / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D040542:Mechanotransduction, Cellular; D008969:Molecular Sequence Data
chemical_list: D029968:Escherichia coli Proteins; D007473:Ion Channels; D008051:Lipid Bilayers; D008244:Lysophosphatidylcholines; C086596:MscL protein, E coli
keywords: critical micelle concentration of LPC; mechanosensation; protein-lipid interaction; spectroscopy