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Voltage Dependence of Conformational Dynamics and Subconducting States of VDAC-1.

dc.contributor.authorBriones, Rodolfo
dc.contributor.authorWeichbrodt, Conrad
dc.contributor.authorPaltrinieri, Licia
dc.contributor.authorMey, Ingo
dc.contributor.authorVillinger, Saskia
dc.contributor.authorGiller, Karin
dc.contributor.authorLange, Adam
dc.contributor.authorZweckstetter, Markus
dc.contributor.authorGriesinger, Christian
dc.contributor.authorBecker, Stefan
dc.contributor.authorSteinem, Claudia
dc.contributor.authorde Groot, Bert L.
dc.date.accessioned2016-10-13T09:16:03Z
dc.date.available2016-10-13T09:16:03Z
dc.date.issued2016-09-20
dc.identifier.citationBriones, Rodolfo; Weichbrodt, Conrad; Paltrinieri, Licia; Mey, Ingo; Villinger, Saskia; Giller, Karin; Lange, Adam; Zweckstetter, Markus; Griesinger, Christian; Becker, Stefan; Steinem, Claudia; de Groot, Bert L (2016): Voltage Dependence of Conformational Dynamics and Subconducting States of VDAC-1. - Biophysical journal, Vol. 111, Nr. 6, p. 1223-34
dc.relation.ISSN1542-0086
dc.identifier.urihttp://resolver.sub.uni-goettingen.de/purl?gs-1/13769
dc.description.abstractThe voltage-dependent anion channel 1 (VDAC-1) is an important protein of the outer mitochondrial membrane that transports energy metabolites and is involved in apoptosis. The available structures of VDAC proteins show a wide β-stranded barrel pore, with its N-terminal α-helix (N-α) bound to its interior. Electrophysiology experiments revealed that voltage, its polarity, and membrane composition modulate VDAC currents. Experiments with VDAC-1 mutants identified amino acids that regulate the gating process. However, the mechanisms for how these factors regulate VDAC-1, and which changes they trigger in the channel, are still unknown. In this study, molecular dynamics simulations and single-channel experiments of VDAC-1 show agreement for the current-voltage relationships of an "open" channel and they also show several subconducting transient states that are more cation selective in the simulations. We observed voltage-dependent asymmetric distortions of the VDAC-1 barrel and the displacement of particular charged amino acids. We constructed conformational models of the protein voltage response and the pore changes that consistently explain the protein conformations observed at opposite voltage polarities, either in phosphatidylethanolamine or phosphatidylcholine membranes. The submicrosecond VDAC-1 voltage response shows intrinsic structural changes that explain the role of key gating amino acids and support some of the current gating hypotheses. These voltage-dependent protein changes include asymmetric barrel distortion, its interaction with the membrane, and significant displacement of N-α amino acids.
dc.languageeng
dc.language.isoeng
dc.relationinfo:eu-repo/grantAgreement/EC/FP7/282008/EU//DYNAMOM
dc.rightsopenAccess
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectvoltage-dependent anion channel 1; VDAC-1; Voltage Dependence
dc.titleVoltage Dependence of Conformational Dynamics and Subconducting States of VDAC-1.
dc.typejournalArticle
dc.identifier.doi10.1016/j.bpj.2016.08.007
dc.type.versionpublishedVersion
dc.bibliographicCitation.volume111
dc.bibliographicCitation.issue6
dc.bibliographicCitation.firstPage1223
dc.bibliographicCitation.lastPage1234
dc.type.subtypejournalArticle
dc.identifier.pmid27653481
dc.relation.euprojectDYNAMOM
dc.description.statuspeerReviewed
dc.bibliographicCitation.journalBiophysical journal


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