Solid-state NMR, electrophysiology and molecular dynamics characterization of human VDAC2
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The voltage-dependent anion channel (VDAC) is the most abundant protein of the outer mitochondrial membrane and constitutes the major pathway for the transport of ADP, ATP, and other metabolites. In this multidisciplinary study we combined solid-state NMR, electrophysiology, and molecular dynamics simulations, to study the structure of the human VDAC isoform 2 in a lipid bilayer environment. We find that the structure of hVDAC2 is similar to the structure of hVDAC1, in line with recent investigations on zfVDAC2. However, hVDAC2 appears to exhibit an increased conformational heterogeneity compared to hVDAC1 which is reflected in broader solid-state NMR spectra and less defined electrophysiological profiles.
KeywordsVoltage-dependent anion channel Membrane proteins Solid-state NMR Molecular dynamics simulations
We thank B. Angerstein for expert technical assistance and R. Briones for help in the initial stages of the project concerning GROMACS. This work was supported by the Max Planck Society, the Leibniz-Institut für Molekulare Pharmakologie, the ERC (grant agreement number 282008 to M.Z.), the DFG (Collaborative research center 803 to A.L., C.G., and M.Z. and Emmy Noether Fellowship to A.L.) and by a Marie Curie fellowship within the 7th EU Framework Program to Z.G.
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