Cited by 588Mitochondrial Function and PathologyProtein Structure and DynamicsEnzyme Structure and Function

Structure of the human voltage-dependent anion channel

Open access
Bayrhuber, Monika, Meins, Thomas, Habeck, Michael, Becker, Stefan, Giller, Karin, Villinger, Saskia, Vonrhein, Clemens, Griesinger, Christian +2 more·2008·Proceedings of the National Academy of Sciences

Abstract

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.

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Crossref · 10.1073/pnas.0808115105

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  • It is unlikely that VDAC itself participates as a cholesterol channel, because the center of its ring-like structure is hydrophilic, suitable for anion transport but unsuitable for hydrophobic molecule transport.

    “It is unlikely that VDAC itself participates as a cholesterol channel, as the center of its ring-like structure is hydrophilic, suitable for anion transport but unsuitable for hydrophobic molecule transport (103, 104).”

    From Adrenal Mitochondria and Steroidogenesis: From Individual Proteins to Functional Protein Assemblies (2016) · cites this paper as [104]

    The 3D Structure of hVDAC1 section describes a barrel-shaped pore with space for small metabolites, and the N-Terminal Helix Is Located Inside the Pore section identifies predominantly hydrophilic residues on the barrel wall (page numbers unavailable). These findings support the structural premise, but the paper does not address cholesterol transport or conclude that VDAC is unsuitable as a cholesterol channel. (LLM, conf=0.85)

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Authors
Bayrhuber, M., Meins, T., Habeck, M., Becker, S., Giller, K., Villinger, S., Vonrhein, C., Griesinger, C., Zweckstetter, M., & Zeth, K.
Affiliations
  • Max Planck Institute for Biophysical Chemistry (DE)
  • Max Planck Institute of Biochemistry (DE)
  • Max Planck Institute for Developmental Biology (DE)
  • Global Phasing (United Kingdom) (GB)
Venue
Proceedings of the National Academy of Sciences
Published
2008-10-07
Volume
105
Issue
40
Pages
15370-15375
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2134087185
Cited by
588
References
37
Citations by year
2026: 17 · 2025: 23 · 2024: 35 · 2023: 27 · 2022: 26 · 2021: 43 · 2020: 39 · 2019: 24 · 2018: 29 · 2017: 29 · 2016: 44 · 2015: 30 · 2014: 40 · 2013: 21 · 2012: 41
FWCI
16.47
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
  • DORA PSI (Paul Scherrer Institute) (submittedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • GRO (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
Funders
  • Deutsche Forschungsgemeinschaft (ZW 71/2-1)
  • Max-Planck-Gesellschaft
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
Keywords
voltage-dependent anion channel, VDAC1, mitochondrial outer membrane, protein structure, Tom40, mitochondrial apoptosis, metabolic flux
MeSH terms
Humans, Models, Molecular, Protein Structure, Secondary, Crystallography, X-Ray, Dimerization, Nuclear Magnetic Resonance, Biomolecular, Voltage-Dependent Anion Channel 1, Hydrophobic and Hydrophilic Interactions

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