Nucleotide interactions of the human voltage-dependent anion channel
| Autor: | Christian Griesinger, Saskia Villinger, Monika Bayrhuber, Markus Zweckstetter, Adam Lange, Karin Giller, Stefan Becker |
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| Rok vydání: | 2014 |
| Předmět: |
chemistry [Adenosine Triphosphate]
Uridine Triphosphate Plasma protein binding genetics [Adenosine Triphosphate] Guanosine triphosphate Biochemistry Protein Structure Secondary Voltage-Dependent Anion Channel 1 chemistry.chemical_compound Adenosine Triphosphate genetics [Guanosine Triphosphate] genetics [Voltage-Dependent Anion Channel 1] Nucleotide genetics [Uridine Triphosphate] genetics [NAD] chemistry.chemical_classification chemistry [Guanosine Triphosphate] 0303 health sciences chemistry [NAD] biology 030302 biochemistry & molecular biology ddc:540 metabolism [NAD] chemistry [Voltage-Dependent Anion Channel 1] VDAC1 protein human Guanosine Triphosphate VDAC1 Molecular Biophysics Protein Binding metabolism [Voltage-Dependent Anion Channel 1] metabolism [Guanosine Triphosphate] Voltage-dependent anion channel NADH binding Stereochemistry Biological Transport Active physiology [Biological Transport Active] 03 medical and health sciences Humans Molecular Biology 030304 developmental biology chemistry [Uridine Triphosphate] metabolism [Uridine Triphosphate] Cell Biology NAD chemistry metabolism [Adenosine Triphosphate] biology.protein Adenosine triphosphate |
| Zdroj: | Journal of Biological Chemistry The journal of biological chemistry 289(19), 13397-13406 (2014). doi:10.1074/jbc.M113.524173 |
| ISSN: | 1083-351X |
| DOI: | 10.1074/jbc.M113.524173 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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