Dynamics of Nucleotides in VDAC Channels: Structure-Specific Noise Generation |
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Authors: | Tatiana K. RostovtsevaAlexander Komarov Sergey M. Bezrukov Marco Colombini |
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Affiliation: | * Department of Biology, University of Maryland, College Park, Maryland 20742 † Laboratory of Physical and Structural Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 USA ‡ St. Petersburg Nuclear Physics Institute, Gatchina 188350, Russia |
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Abstract: | Nucleotide penetration into the voltage-dependent mitochondrial ion channel (VDAC) reduces single-channel conductance and generates excess current noise through a fully open channel. VDAC channels were reconstituted into planar phospholipid membranes bathed in 1.0 M NaCl. At a given nucleotide concentration, the average decrease in small-ion channel conductance induced by mononucleotides ATP, ADP, AMP, and UTP and dinucleotides β- and α-NADH, NAD, and NADPH are very close. However, the excess current noise is about seven times higher in the presence of NADPH than in the presence of ATP and is about 40 times higher than in the presence of UTP. The nucleotide-generated low-frequency noise obeys the following sequence: β-NADPH > β-NADH = α-NADH > ATP > ADP > β-NAD ≥ AMP > UTP. Measurements of bulk-phase diffusion coefficients and of the effective charge of the nucleotides in 1.0 M NaCl suggest that differences in size and charge cannot be the major factors responsible for the ability to generate current noise. Thus, although the ability of nucleotides to partition into the channel’s pore, as assessed by the reduction in conductance, is very similar, the ability to generate current noise involves a detailed recognition of the three-dimensional structure of the nucleotide by the VDAC channel. A possible mechanism for this selectivity is two noise-generating processes operating in parallel. |
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