The Single Residue K12 Governs the Exceptional Voltage Sensitivity of Mitochondrial Voltage-Dependent Anion Channel Gating.

ABSTRACT: The voltage-dependent anion channel (VDAC) is a β-barrel channel of the mitochondrial outer membrane (MOM) that passively transports ions, metabolites, polypeptides, and single-stranded DNA. VDAC responds to a transmembrane potential by "gating," i.e. transitioning to one of a variety of low-conducting states of unknown structure. The gated state results in nearly complete suppression of multivalent mitochondrial metabolite (such as ATP and ADP) transport, while enhancing calcium transport. Voltage gating is a universal property of β-barrel channels, but VDAC gating is anomalously sensitive to transmembrane potential. Here, we show that a single residue in the pore interior, K12, is responsible for most of VDAC's voltage sensitivity. Using the analysis of over 40 μs of atomistic molecular

SUBMITTER: Ngo VA 

PROVIDER: S-EPMC12293989 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature