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Solution Structure of the Integral Human Membrane Protein VDAC-1 in Detergent Micelles

Sebastian Hiller, Robert G. Garces, Thomas J. Malia, Vladislav Y. Orekhov, Marco Colombini and Gerhard Wagner
Science
New Series, Vol. 321, No. 5893 (Aug. 29, 2008), pp. 1206-1210
Stable URL: http://www.jstor.org/stable/20144703
Page Count: 5
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Solution Structure of the Integral Human Membrane Protein VDAC-1 in Detergent Micelles
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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 β 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 $\text{Bcl}-\text{x}_{\text{L}}$, for reduced β--nicotinamide adenine dinucleotide, and for cholesterol. $\text{Bcl}-\text{x}_{\text{L}}$ interacts with the VDAC barrel laterally at strands 17 and 18.

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