Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 289, Issue 19, Pages 13397-13406Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M113.524173
Keywords
ATP; Membrane Proteins; NMR; Nucleotide; Organic Anion Channels; Interactions
Categories
Funding
- Fonds der Chemischen Industrie
- Deutsche Forschungsgemeinschaft (DFG)
- DFG collaborative research center SFB803
- ERC [282008]
- European Research Council (ERC) [282008] Funding Source: European Research Council (ERC)
Ask authors/readers for more resources
Background: Human VDAC1 mediates and controls the transport of metabolites across the outer mitochondrial membrane. Results: The N-terminal helix of hVDAC1 is involved in binding to charged forms of ATP, UTP, and GTP with an important contribution from lysine 20. Conclusion: Weak binding of ATP confers specificity for ATP transport. Significance: ATP interaction mapped at residue resolution supports metabolite selectivity of VDAC. 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 Mg2+-complexed ATP form is possible.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available