Solution structure of the integral human membrane protein VDAC-1 in detergent micelles

Science. 2008 Aug 29;321(5893):1206-10. doi: 10.1126/science.1161302.


The voltage-dependent anion channel (VDAC) mediates trafficking of small molecules and ions across the eukaryotic outer mitochondrial membrane. VDAC also interacts with antiapoptotic proteins from the Bcl-2 family, and this interaction inhibits release of apoptogenic proteins from the mitochondrion. We present the nuclear magnetic resonance (NMR) solution structure of recombinant human VDAC-1 reconstituted in detergent micelles. It forms a 19-stranded beta barrel with the first and last strand parallel. The hydrophobic outside perimeter of the barrel is covered by detergent molecules in a beltlike fashion. In the presence of cholesterol, recombinant VDAC-1 can form voltage-gated channels in phospholipid bilayers similar to those of the native protein. NMR measurements revealed the binding sites of VDAC-1 for the Bcl-2 protein Bcl-x(L), for reduced beta-nicotinamide adenine dinucleotide, and for cholesterol. Bcl-x(L) interacts with the VDAC barrel laterally at strands 17 and 18.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Cholesterol / metabolism
  • Detergents
  • Dimethylamines
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Ion Channel Gating
  • Lipid Bilayers
  • Micelles
  • Molecular Sequence Data
  • NAD / metabolism
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Conformation
  • Protein Folding
  • Protein Structure, Secondary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Static Electricity
  • Voltage-Dependent Anion Channel 1 / chemistry*
  • Voltage-Dependent Anion Channel 1 / metabolism*
  • bcl-X Protein / metabolism


  • Detergents
  • Dimethylamines
  • Lipid Bilayers
  • Micelles
  • Recombinant Proteins
  • VDAC1 protein, human
  • bcl-X Protein
  • NAD
  • dodecyldimethylamine oxide
  • Cholesterol
  • Voltage-Dependent Anion Channel 1

Associated data

  • PDB/2K4T