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Nucleotide interactions of the human voltage-dependent anion channel.

ABSTRACT: The voltage-dependent anion channel (VDAC) mediates and gates the flux of metabolites and ions across the outer mitochondrial membrane and is a key player in cellular metabolism and apoptosis. Here we characterized the binding of nucleotides to human VDAC1 (hVDAC1) on a single-residue level using NMR spectroscopy and site-directed mutagenesis. We find that hVDAC1 possesses one major binding region for ATP, UTP, and GTP that partially overlaps with a previously determined NADH binding site. This nucleotide binding region is formed by the N-terminal ?-helix, the linker connecting the helix to the first ?-strand and adjacent barrel residues. hVDAC1 preferentially binds the charged forms of ATP, providing support for a mechanism of metabolite transport in which direct binding to the charged form exerts selectivity while at the same time permeation of the Mg(2+)-complexed ATP form is possible.

SUBMITTER: Villinger S

PROVIDER: S-EPMC4036348 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Nucleotide interactions of the human voltage-dependent anion channel.

Villinger Saskia S Giller Karin K Bayrhuber Monika M Lange Adam A Griesinger Christian C Becker Stefan S Zweckstetter Markus M

The Journal of biological chemistry 20140325 19

The voltage-dependent anion channel (VDAC) mediates and gates the flux of metabolites and ions across the outer mitochondrial membrane and is a key player in cellular metabolism and apoptosis. Here we characterized the binding of nucleotides to human VDAC1 (hVDAC1) on a single-residue level using NMR spectroscopy and site-directed mutagenesis. We find that hVDAC1 possesses one major binding region for ATP, UTP, and GTP that partially overlaps with a previously determined NADH binding site. This ...[more]

PMID: 24668813

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