Solution structure of the integral human membrane protein VDAC-1 in detergent micelles
By S. Hiller, R. Garces, T. Malia, V. Orekhov, M. Colombini, G. Wagner. 2008
675 citations recorded by the source corpus.
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 Bcl-xL, for reduced β–nicotinamide adenine dinucleotide, and for cholesterol. Bcl-xL interacts with the VDAC barrel laterally at strands 17 and 18.
Subfields: Molecular Biology
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In Molecular Biology
- Andriy Kryshtafovych
- Torsten Schwede
- Krzysztof Fidelis
- Anna Tramontano
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- John Moult
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- Liam J. McGuffin
Citations in the corpus
- Critical Assessment of Methods of Protein Structure Prediction (CASP) – Progress and New directions in Round XI (2016, background): “27–31 However, perdeuteration also reduces the number of 1 H-1 H NOE-based distance restraints that can be obtained, providing models that are less accurate and precise, and in many cases precluding structure determination by conventional NMR structural modeling techniques alto-gether.”
- Protein structure determination by combining sparse NMR data with evolutionary couplings (2015, neutral): “Such “sparse NMR data” can generally be obtained for perdeuterated proteins with molecular weights as large as 40– 60 kDa 22–24 , and have been used in exceptional cases to determine chain folds for proteins as large as 82 kDa 25,26 .”
- Determination of solution structures of proteins up to 40 kDa using CS-Rosetta with sparse NMR data from deuterated samples (2012, neutral): “Perdeuteration is generally required for studies of larger proteins (11 – 14), particularly membrane proteins (15, 16).”