Voltage-dependent anion channel
Encyclopedia
Voltage-dependent anion channels are a class of porin
ion channel
located on the outer mitochondrial membrane
.
This major protein of the outer mitochondrial membrane of eukaryotes. It forms a voltage-dependent anion-selective channel (VDAC) that behaves as a general diffusion pore for small hydrophilic molecules. The channel adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV. VDAC facilitates the exchange of ions and molecules between mitochondria and cytosol and is regulated by the interactions with other proteins and small molecules.
Since its discovery in 1976, extensive function and structure analysis of VDAC proteins has been conducted. A prominent feature of the pore emerged: when reconstituted into planar lipid bilayers, there is a voltage-dependent switch between an anion-selective high-conductance state with high metabolite flux and a cation-selective low-conductance state with limited passage of metabolites.
More than 30 years after its initial discovery, in 2008, three independent structural projects of VDAC-1 were completed. The first was solved by multi-dimensional NMR spectroscopy. The second applied a hybrid approach using crystallographic data. The third was for mouse VDAC-1 crystals determined by X-ray crystallographic techniques. The three projects of the 3D structures of VDAC-1 revealed many structural features. First, VDAC-1 represents a new structural class of outer membrane β-barrel proteins with an odd number of strands. Another aspect is that the negatively charged side chain of residue E73 is oriented towards the hydrophobic membrane environment. The 19-stranded 3D structure obtained under different experimental sources by three different laboratories fits the EM and AFM data from native membrane sources and represents a biologically relevant state of VDAC-1.
Human proteins containing this domain include TOMM40
, TOMM40L
, VDAC1
, VDAC2
, and VDAC3
.
Porin (protein)
Porins are beta barrel proteins that cross a cellular membrane and act as a pore through which molecules can diffuse. Unlike other membrane transport proteins, porins are large enough to allow passive diffusion, i.e., they act as channels that are specific to different types of molecules...
ion channel
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
located on the outer mitochondrial membrane
Outer mitochondrial membrane
thumb|300px|Mitochondria structure :1) [[Inner membrane]]2) Outer membrane3) [[Crista]]4) [[Matrix |Matrix]]The outer mitochondrial membrane, which encloses the entire organelle, has a protein-to-phospholipid ratio similar to the eukaryotic plasma membrane...
.
This major protein of the outer mitochondrial membrane of eukaryotes. It forms a voltage-dependent anion-selective channel (VDAC) that behaves as a general diffusion pore for small hydrophilic molecules. The channel adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV. VDAC facilitates the exchange of ions and molecules between mitochondria and cytosol and is regulated by the interactions with other proteins and small molecules.
Structure
This protein contains about 280 amino acids and its sequence is composed of between 12 to 16 beta-strands that span the mitochondrial outer membrane.Since its discovery in 1976, extensive function and structure analysis of VDAC proteins has been conducted. A prominent feature of the pore emerged: when reconstituted into planar lipid bilayers, there is a voltage-dependent switch between an anion-selective high-conductance state with high metabolite flux and a cation-selective low-conductance state with limited passage of metabolites.
More than 30 years after its initial discovery, in 2008, three independent structural projects of VDAC-1 were completed. The first was solved by multi-dimensional NMR spectroscopy. The second applied a hybrid approach using crystallographic data. The third was for mouse VDAC-1 crystals determined by X-ray crystallographic techniques. The three projects of the 3D structures of VDAC-1 revealed many structural features. First, VDAC-1 represents a new structural class of outer membrane β-barrel proteins with an odd number of strands. Another aspect is that the negatively charged side chain of residue E73 is oriented towards the hydrophobic membrane environment. The 19-stranded 3D structure obtained under different experimental sources by three different laboratories fits the EM and AFM data from native membrane sources and represents a biologically relevant state of VDAC-1.
Examples
Yeast contains two members of this family (genes POR1 and POR2); vertebrates have at least three members (genes VDAC1, VDAC2 and VDAC3).Human proteins containing this domain include TOMM40
TOMM40
Translocase of outer mitochondrial membrane 40 homolog , also known as TOMM40, is a protein which in humans is encoded by the TOMM40 gene.-Function:...
, TOMM40L
TOMM40L
Mitochondrial import receptor subunit TOM40B is a protein that in humans is encoded by the TOMM40L gene.-Further reading:...
, VDAC1
VDAC1
Voltage-dependent anion-selective channel protein 1 is a protein that in humans is encoded by the VDAC1 gene.-Interactions:VDAC1 has been shown to interact with Gelsolin, BCL2-like 1, PRKCE, Bcl-2-associated X protein and DYNLT3.- External links :...
, VDAC2
VDAC2
Voltage-dependent anion-selective channel protein 2 is a protein that in humans is encoded by the VDAC2 gene. The protein encoded by this gene is a voltage-dependent anion channel.VDAC2 is involved in the regulation of mitochondrial apoptosis....
, and VDAC3
VDAC3
Voltage-dependent anion-selective channel protein 3 is a protein that in humans is encoded by the VDAC3 gene.VDAC3 orthologs have been identified in most mammals for which complete genome data are available....
.