Structure of the human voltage-dependent anion channel

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 105; no. 40; pp. 15370 - 15375
• Main Authors: Bayrhuber, Monika, Meins, Thomas, Habeck, Michael, Becker, Stefan, Giller, Karin, Villinger, Saskia, Vonrhein, Clemens, Griesinger, Christian, Zweckstetter, Markus, Zeth, Kornelius
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 07.10.2008; National Acad Sciences
• Subjects: Apoptosis; Bioinformatics; Biological Sciences; Chemical equilibrium; Crystal structure; Crystallography; Crystallography, X-Ray; Dimerization; Dimers; Electric potential; Electron density; Human subjects; Humans; Hydrophobic and Hydrophilic Interactions; Ions; Membrane proteins; mitochondrial membrane; Models, Molecular; Mothers; NMR; Nuclear magnetic resonance; nuclear magnetic resonance spectroscopy; Nuclear Magnetic Resonance, Biomolecular; physiological transport; Porins; Protein Structure, Secondary; Proteins; Spectrum analysis; Voltage dependent anion channels; Voltage-Dependent Anion Channel 1 - chemistry; Voltage-Dependent Anion Channel 1 - metabolism; X-ray diffraction
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.0808115105

The voltage-dependent anion channel (VDAC), also known as mitochondrial porin, is the most abundant protein in the mitochondrial outer membrane (MOM). VDAC is the channel known to guide the metabolic flux across the MOM and plays a key role in mitochondrially induced apoptosis. Here, we present the 3D structure of human VDAC1, which was solved conjointly by NMR spectroscopy and x-ray crystallography. Human VDAC1 (hVDAC1) adopts a β-barrel architecture composed of 19 β-strands with an α-helix located horizontally midway within the pore. Bioinformatic analysis indicates that this channel architecture is common to all VDAC proteins and is adopted by the general import pore TOM40 of mammals, which is also located in the MOM.