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Probing Tubulin-Blocked State of VDAC by Varying Membrane Surface Charge

dc.contributor.authorGurnev, Philip A.
dc.contributor.authorQueralt-Martín, María
dc.contributor.authorAguilella, Vicente
dc.contributor.authorRostovtseva, Tatiana K.
dc.date.accessioned2013-06-13T09:31:42Z
dc.date.available2013-06-13T09:31:42Z
dc.date.issued2012-05
dc.identifier.urihttp://hdl.handle.net/10234/67077
dc.descriptionReversible blockage of the voltage-dependent anion channel (VDAC) of the mitochondrial outer membrane by dimeric tubulin is being recognized as a potent regulator of mitochondrial respiration. The tubulin-blocked state of VDAC is impermeant for ATP but only partially closed for small ions. This residual conductance allows studying the nature of the tubulin-blocked state in single-channel reconstitution experiments. Here we probe this state by changing lipid bilayer charge from positive to neutral to negative. We find that voltage sensitivity of the tubulin-VDAC blockage practically does not depend on the lipid charge and salt concentration with the effective gating charge staying within the range of 10–14 elementary charges. At physiologically relevant low salt concentrations, the conductance of the tubulin-blocked state is decreased by positive and increased by negative charge of the lipids, whereas the conductance of the open channel is much less sensitive to this param- eter. Such a behavior supports the model in which tubulin’s negatively charged tail enters the VDAC pore, inverting its anionic selectivity to cationic and increasing proximity of ion pathways to the nearest lipid charges as compared with the open state of the channel.ca_CA
dc.format.extent7 p.ca_CA
dc.format.mimetypeapplication/pdfca_CA
dc.language.isoengca_CA
dc.publisherBiophysical Societyca_CA
dc.relation.isPartOfByophysical Journal, v. 102, issue 9 (May 2012)ca_CA
dc.rights.urihttp://rightsstatements.org/vocab/CNE/1.0/*
dc.subjectvdacca_CA
dc.subjectchargeca_CA
dc.subjecttubulinca_CA
dc.subjectstateca_CA
dc.subjectchannel selectivity inversionca_CA
dc.subjectlipidca_CA
dc.subjectsurface chargeca_CA
dc.subjectconductanceca_CA
dc.subjectmembrane surfaceca_CA
dc.subjectmembraneca_CA
dc.subjectprobeca_CA
dc.subjectmitochondrialca_CA
dc.subjectsalt concentrationca_CA
dc.subjectsaltca_CA
dc.subjectblockageca_CA
dc.titleProbing Tubulin-Blocked State of VDAC by Varying Membrane Surface Chargeca_CA
dc.typeinfo:eu-repo/semantics/articleca_CA
dc.identifier.doihttp://dx.doi.org/10.1016/j.bpj.2012.03.058
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_CA
dc.type.versioninfo:eu-repo/semantics/publishedVersion


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