• VDAC's

    Representative parallel recording from 3 VDAC channel measured on the Orbit mini

2016 - Voltage Dependence of Conformational Dynamics and Subconducting States of VDAC-1

icon pap  Port-a-Patch publication in Biophysical Journal (2016)

Authors: 
Briones R., Weichbrodt C., Paltrinieri L., Mey I., Villinger S., Giller K., Lange A., Zweckstetter M., Griesinger C., Becker S., Steinem C., de Groot B.L.

 

Journal: 
Biophysical Journal 2016 Sep 20, 111:1223-1234


Abstract: 

The voltage-dependent anion channel 1 (VDAC-1) is an important protein of the outer mitochondrial membrane that transports energy metabolites and is involved in apoptosis. The available structures of VDAC proteins show a wide β-stranded barrel pore, with its N-terminal α-helix (N-α) bound to its interior. Electrophysiology experiments revealed that voltage, its polarity, and membrane composition modulate VDAC currents. Experiments with VDAC-1 mutants identified amino acids that regulate the gating process. However, the mechanisms for how these factors regulate VDAC-1, and which changes they trigger in the channel, are still unknown. In this study, molecular dynamics simulations and single-channel experiments of VDAC-1 show agreement for the current-voltage relationships of an “open” channel and they also show several subconducting transient states that are more cation selective in the simulations. We observed voltage-dependent asymmetric distortions of the VDAC-1 barrel and the displacement of particular charged amino acids. We constructed conformational models of the protein voltage response and the pore changes that consistently explain the protein conformations observed at opposite voltage polarities, either in phosphatidylethanolamine or phosphatidylcholine membranes. The submicrosecond VDAC-1 voltage response shows intrinsic structural changes that explain the role of key gating amino acids and support some of the current gating hypotheses. These voltage-dependent protein changes include asymmetric barrel distortion, its interaction with the membrane, and significant displacement of N-α amino acids.


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