title: Solution structure of the integral human membrane protein VDAC-1 in detergent micelles.
abstract: 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.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hiller
authors.forename: Robert G
authors.initials: RG
authors.lastname: Garces
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Malia
authors.forename: Vladislav Y
authors.initials: VY
authors.lastname: Orekhov
authors.forename: Marco
authors.initials: M
authors.lastname: Colombini
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wagner