Molecular Plasticity of the Human Voltage-Dependent Anion Channel Embedded Into a Membrane.
- Ge L Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule (ETH) Zürich, Mattenstrasse 26, 4058 Basel, Switzerland.
- Villinger S Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
- Mari SA Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule (ETH) Zürich, Mattenstrasse 26, 4058 Basel, Switzerland.
- Giller K Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
- Griesinger C Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
- Becker S Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
- Müller DJ Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule (ETH) Zürich, Mattenstrasse 26, 4058 Basel, Switzerland. Electronic address: daniel.mueller@bsse.ethz.ch.
- Zweckstetter M Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany; Structural Biology in Dementia, German Center for Neurodegenerative Diseases (DZNE), Von-Siebold-Strasse 3a, 37075 Göttingen, Germany; Department of Neurology, University Medical Center Göttingen, University of Göttingen, Am Waldweg 33, 37073 Göttingen, Germany. Electronic address: markus.zweckstetter@dzne.de.
- 2016-03-30
Published in:
- Structure (London, England : 1993). - 2016
NMR spectroscopy
atomic force microscopy
calcium dependency
conformational variability
human voltage-dependent anion channel
integral membrane protein
single-molecule force spectroscopy
structural flexibility
Calcium
Humans
Kinetics
Mitochondrial Membranes
Models, Molecular
Nuclear Magnetic Resonance, Biomolecular
Protein Structure, Secondary
Single Molecule Imaging
Voltage-Dependent Anion Channel 1
English
The voltage-dependent anion channel (VDAC) regulates the flux of metabolites and ions across the outer mitochondrial membrane. Regulation of ion flow involves conformational transitions in VDAC, but the nature of these changes has not been resolved to date. By combining single-molecule force spectroscopy with nuclear magnetic resonance spectroscopy we show that the β barrel of human VDAC embedded into a membrane is highly flexible. Its mechanical flexibility exceeds by up to one order of magnitude that determined for β strands of other membrane proteins and is largest in the N-terminal part of the β barrel. Interaction with Ca(2+), a key regulator of metabolism and apoptosis, considerably decreases the barrel's conformational variability and kinetic free energy in the membrane. The combined data suggest that physiological VDAC function depends on the molecular plasticity of its channel.
- Language
-
- English
- Open access status
- bronze
- Identifiers
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- DOI 10.1016/j.str.2016.02.012
- PMID 27021164
- Persistent URL
- https://sonar.ch/global/documents/223304
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