Solid-state NMR, electrophysiology and molecular dynamics characterization of human VDAC2.
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.
Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077, Göttingen, Germany.
Zrinka
Z
Gattin
Robert
R
Schneider
Yvonne
Y
Laukat
Karin
K
Giller
Elke
E
Maier
Markus
M
Zweckstetter
Christian
C
Griesinger
Roland
R
Benz
Stefan
S
Becker
Adam
A
Lange
D000595:Amino Acid Sequence; D055724:Electrophysiological Phenomena / Q000502:physiology*; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D008928:Mitochondria / Q000378:metabolism; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D020033:Protein Isoforms / Q000737:chemistry; D016415:Sequence Alignment; D050995:Voltage-Dependent Anion Channel 1 / Q000648:ultrastructure*; D050996:Voltage-Dependent Anion Channel 2 / Q000737:chemistry* / Q000648:ultrastructure*
D008051:Lipid Bilayers; D020033:Protein Isoforms; C494762:VDAC1 protein, human; C494765:VDAC2 protein, human; D050996:Voltage-Dependent Anion Channel 2; D050995:Voltage-Dependent Anion Channel 1