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29  structures 1440  species 0  interactions 6725  sequences 93  architectures

Family: Porin_3 (PF01459)

Summary: Eukaryotic porin

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Voltage-dependent anion channel". More...

Voltage-dependent anion channel Edit Wikipedia article

Eukaryotic porin
Human Voltage-Dependent Anion Channel Protein Structure.png
Crystal Structure of the Human Voltage-Dependent Anion Channel. The arrows denote the antiparallel beta sheets that form the characteristic beta-barrel
Identifiers
SymbolPorin_3
PfamPF01459
InterProIPR001925
PROSITEPDOC00483
TCDB1.B.8
OPM superfamily189
OPM protein3emn
CDDcd07306

Voltage-dependent anion channels, or mitochondrial porins, are a class of porin ion channel located on the outer mitochondrial membrane.[1][2] There is debate as to whether or not this channel is expressed in the cell surface membrane.[3][4][5]

This major protein of the outer mitochondrial membrane of eukaryotes forms a voltage-dependent anion-selective channel (VDAC) that behaves as a general diffusion pore for small hydrophilic molecules.[6][7][8][9] 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.[10]

Structure

This protein contains about 280 amino acids and forms a beta barrel which spans the mitochondrial outer membrane.[11][12]

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.[10]

Mechanism

At membrane potentials exceeding 30 mV (positive or negative), VDAC assumes a closed state, and transitions to its open state once the voltage drops below this threshold. Although both states allow passage of simple salts, VDAC is much more stringent with organic anions, a category into which most metabolites fall.[13] The precise mechanism for coupling voltage changes to conformational changes within the protein has not yet been worked out, but studies by Thomas et al. suggest that when the protein transitions to the closed form, voltage changes lead to the removal of a large section of the protein from the channel and decrease effective pore radius.[14] Several lysine residues, as well as Glu-152, have been implicated as especially important sensor residues within the protein.[15]

Biological function

The voltage-dependent ion channel plays a key role in regulating metabolic and energetic flux across the outer mitochondrial membrane. It is involved in the transport of ATP, ADP, pyruvate, malate, and other metabolites, and thus communicates extensively with enzymes from metabolic pathways.[13] The ATP-dependent cytosolic enzymes hexokinase, glucokinase, and glycerol kinase, as well as the mitochondrial enzyme creatine kinase, have all been found to bind to VDAC. This binding puts them in close proximity to ATP released from the mitochondria. In particular, the binding of hexokinase is presumed to play a key role in coupling glycolysis to oxidative phosphorylation.[14] Additionally, VDAC is an important regulator of Ca2+ transport in and out of the mitochondria. Because Ca2+ is a cofactor for metabolic enzymes such as pyruvate dehydrogenase and isocitrate dehydrogenase, energetic production and homeostasis are both affected by VDAC’s permeability to Ca2+.[16]

Disease relevance

VDAC has also been shown to play a role in apoptosis.[17] During apoptosis, increased permeability of VDAC allows for the release of apoptogenic factors such as cytochrome c. Although cyt. c plays an essential role in oxidative phosphorylation within the mitochondrion, in the cytosol it activates proteolytic enzymes called caspases, which play a major role in cell death.[18] Although the mechanism for VDAC-facilitated cyt. c release has not yet been fully elucidated, some research suggests that oligomerization between individual subunits may create a large flexible pore through which cyt. c can pass.[19] A more important factor is that release of cyt c. is also regulated by the Bcl-2 protein family: Bax interacts directly with VDAC to increase pore size and promote cyt. c release, while anti-apoptotic Bcl-xL produces the exact opposite effect.[20] In fact, it has been shown that antibodies that inhibit VDAC also interfere with Bax-mediated cyt. c release in both isolated mitochondria and whole cells.[21] This key role in apoptosis suggests VDAC as a potential target for chemotherapeutic drugs.

Examples

Yeast contains two members of this family (genes POR1 and POR2); vertebrates have at least three members (genes VDAC1, VDAC2 and VDAC3).[11]

Humans, like most higher eukaryotes, encode three different VDACs; VDAC1, VDAC2, and VDAC3. Together with TOMM40 and TOMM40L they represent a family of evolutionarily related β-barrels.[22]

Plants have the largest number of VDACs. Arabidopsis encode four different VDACs but this number can be larger in other species.[23]

References

  1. ^ Hoogenboom BW, Suda K, Engel A, Fotiadis D (2007). "The supramolecular assemblies of voltage-dependent anion channels in the native membrane". J. Mol. Biol. 370 (2): 246–55. doi:10.1016/j.jmb.2007.04.073. PMID 17524423.
  2. ^ Blachly-Dyson, E; Forte, M (September 2001). "VDAC channels". IUBMB Life. 52 (3–5): 113–8. doi:10.1080/15216540152845902. PMID 11798022.
  3. ^ Sabirov RZ, Merzlyak PG (June 2012). "Plasmalemmal VDAC controversies and maxi-anion channel puzzle". Biochim. Biophys. Acta. 1818 (6): 1570–80. doi:10.1016/j.bbamem.2011.09.024. PMID 21986486.
  4. ^ De Pinto, V.; Messina, A.; Lane, D. J. R.; Lawen, A. (2010). "Voltage-dependent anion-selective channel (VDAC) in the plasma membrane". FEBS Letters. 584 (9): 1793–1799. doi:10.1016/j.febslet.2010.02.049. PMID 20184885.
  5. ^ Niehage, C.; Steenblock, C.; Pursche, T.; Bornhäuser, M.; Corbeil, D.; Hoflack, B. (2011). Borlongan, Cesario V (ed.). "The Cell Surface Proteome of Human Mesenchymal Stromal Cells". PLoS ONE. 6 (5): e20399. Bibcode:2011PLoSO...620399N. doi:10.1371/journal.pone.0020399. PMC 3102717. PMID 21637820.
  6. ^ Benz R (1994). "Permeation of hydrophilic solutes through mitochondrial outer membranes: review on mitochondrial porins". Biochim. Biophys. Acta. 1197 (2): 167–196. doi:10.1016/0304-4157(94)90004-3. PMID 8031826.
  7. ^ Mannella CA (1992). "The 'ins' and 'outs' of mitochondrial membrane channels". Trends Biochem. Sci. 17 (8): 315–320. doi:10.1016/0968-0004(92)90444-E. PMID 1384178.
  8. ^ Dihanich M (1990). "The biogenesis and function of eukaryotic porins". Experientia. 46 (2): 146–153. doi:10.1007/BF02027310. PMID 1689252.
  9. ^ Forte M, Guy HR, Mannella CA (1987). "Molecular genetics of the VDAC ion channel: structural model and sequence analysis" (PDF). J. Bioenerg. Biomembr. 19 (4): 341–350. doi:10.1007/BF00768537. PMID 2442148.
  10. ^ a b Hiller S, Abramson J, Mannella C, Wagner G, Zeth K (September 2010). "The 3D structures of VDAC represent a native conformation". Trends Biochem. Sci. 35 (9): 514–21. doi:10.1016/j.tibs.2010.03.005. PMC 2933295. PMID 20708406.
  11. ^ a b Sampson MJ, Lovell RS, Davison DB, Craigen WJ (1996). "A novel mouse mitochondrial voltage-dependent anion channel gene localizes to chromosome 8". Genomics. 36 (1): 192–196. doi:10.1006/geno.1996.0445. PMID 8812436.
  12. ^ Zeth K (2010). "Structure and evolution of mitochondrial outer membrane proteins of beta-barrel topology". Biochim. Biophys. Acta. 1797 (6–7): 1292–9. doi:10.1016/j.bbabio.2010.04.019. PMID 20450883.
  13. ^ a b Blachly-Dyson, E. & Forte, M. (2001). "VDAC Channels". IUBMB Life. 52 (3–5): 113–18. doi:10.1080/15216540152845902. PMID 11798022.
  14. ^ a b Colombini M, Blachly-Dyson E, Forte M (1996). "VDAC, a channel in the outer mitochondrial membrane". Ion Channels. 4: 169–202. PMID 8744209.
  15. ^ Thomas L, Blachly-Dyson E, Colombini M, Forte M (June 1993). "Mapping of residues forming the voltage sensor of the voltage-dependent anion-selective channel". Proc. Natl. Acad. Sci. U.S.A. 90 (12): 5446–9. Bibcode:1993PNAS...90.5446T. doi:10.1073/pnas.90.12.5446. PMC 46737. PMID 7685903.
  16. ^ Shoshan-Barmatz V; Gincel D. (2003). "The voltage-dependent anion channel: characterization, modulation, and role in mitochondrial function in cell life and death". Cell Biochem. Biophys. 39 (3): 279–92. doi:10.1385/CBB:39:3:279. PMID 14716081.
  17. ^ Lemasters JJ; Holmuhamedov E. (2006). "Voltage-dependent anion channel (VDAC) as mitochondrial governator--thinking outside the box". Biochim. Biophys. Acta. 1762 (2): 181–90. doi:10.1016/j.bbadis.2005.10.006. PMID 16307870.
  18. ^ Tsujimoto Y, Shimizu S (2002). "The voltage-dependent anion channel: an essential player in apoptosis". Biochimie. 84 (2–3): 187–93. doi:10.1016/S0300-9084(02)01370-6. PMID 12022949.
  19. ^ Zalk R; Israelson A; Garty ES; Azoulay-Zohar H; Shoshan-Barmatz V. (2005). "Oligomeric states of the voltage-dependent anion channel and cytochrome c release from mitochondria". Biochem. J. 386 (1): 73–83. doi:10.1042/BJ20041356. PMC 1134768. PMID 15456403.
  20. ^ Shimizu S; Narita M; Tsujimoto Y. (1999). "Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC". Nature. 399 (6735): 483–7. Bibcode:1999Natur.399..483S. doi:10.1038/20959. PMID 10365962.
  21. ^ Shimizu S; Matsuoka Y; Shinohara Y; Yoneda Y; Tsujimoto Y. (2001). "Essential role of voltage-dependent anion channel in various forms of apoptosis in mammalian cells". J. Cell Biol. 152 (2): 237–50. doi:10.1083/jcb.152.2.237. PMC 2199613. PMID 11266442.
  22. ^ Bay DC, Hafez M, Young MJ, Court DA (June 2012). "Phylogenetic and coevolutionary analysis of the β-barrel protein family comprised of mitochondrial porin (VDAC) and Tom40". Biochim. Biophys. Acta. 1818 (6): 1502–19. doi:10.1016/j.bbamem.2011.11.027. PMID 22178864.
  23. ^ Homblé F, Krammer E, Prevost M (June 2012). "Plant VDAC: facts and speculations". Biochim. Biophys. Acta. 1818 (6): 1486–501. doi:10.1016/j.bbamem.2011.11.028. PMID 22155681.

External links

This article incorporates text from the public domain Pfam and InterPro: IPR001925

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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Eukaryotic porin Provide feedback

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External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR027246

This entry represents both eukaryotic mitochondrial porins and Tom40 proteins.

Eukaryotic mitochondrial porins are voltage-dependent anion-selective channels (VDAC) that behave as general diffusion pores for small hydrophilic molecules [ PUBMED:8031826 , PUBMED:1384178 , PUBMED:1689252 , PUBMED:2442148 ]. The channels adopt an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV. The eukaryotic mitochondrial porins are beta-barrel proteins, composed of between 12 to 16 beta-strands that span the mitochondrial outer membrane. Yeast contains two members of this family (genes POR1 and POR2); vertebrates have at least three members (genes VDAC1, VDAC2 and VDAC3) [ PUBMED:8812436 ]. They are related to the mitochondrial import receptor subunit Tom40 proteins, sharing a common evolutionary origin and structure [ PUBMED:22178864 ].

Tom40 is a mitochondrion outer membrane protein and a component of the TOM (translocator of the outer mitochondrial membrane) complex, which is essential for import of protein precursors into mitochondria [ PUBMED:10427088 ]. In Saccharomyces cerevisiae, TOM complex is composed of the subunits Tom70, Tom40, Tom22, Tom20, Tom7, Tom6, and Tom5 [ PUBMED:1327874 , PUBMED:9774667 ]. Tom40 is an integral membrane protein and the main structural component of the protein-conducting channel formed by the TOM complex [ PUBMED:14595396 ]. It is stabilised by other components, such as Tom5, Tom6, and Tom7 [ PUBMED:11866524 ].

Gene Ontology

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Domain organisation

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  Seed
(68)
Full
(6725)
Representative proteomes UniProt
(11229)
RP15
(993)
RP35
(2856)
RP55
(5250)
RP75
(7090)
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  Seed
(68)
Full
(6725)
Representative proteomes UniProt
(11229)
RP15
(993)
RP35
(2856)
RP55
(5250)
RP75
(7090)
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Curation and family details

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Curation View help on the curation process

Seed source: Prodom_3211 (release 99.1) & Pfam-B__3211 (release 7.5)
Previous IDs: Euk_porin;
Type: Family
Sequence Ontology: SO:0100021
Author: Bateman A
Number in seed: 68
Number in full: 6725
Average length of the domain: 242.40 aa
Average identity of full alignment: 23 %
Average coverage of the sequence by the domain: 84.07 %

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HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 28.4 28.4
Trusted cut-off 28.4 28.4
Noise cut-off 28.3 28.2
Model length: 273
Family (HMM) version: 24
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Species distribution

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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Porin_3 domain has been found. There are 29 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0P0V1K5 View 3D Structure Click here
A0A0R0FS37 View 3D Structure Click here
A0A0R0FS37 View 3D Structure Click here
A0A1D6EPA8 View 3D Structure Click here
A0A1D6FWS5 View 3D Structure Click here
A0A1D6FYA4 View 3D Structure Click here
A0A1D6I2X6 View 3D Structure Click here
A0A1D6JN63 View 3D Structure Click here
A0A1D6JN64 View 3D Structure Click here
A0A1D6JS28 View 3D Structure Click here
A0A1D6MQU1 View 3D Structure Click here
A0A1D6MSW8 View 3D Structure Click here
A0A1D6PJM4 View 3D Structure Click here
A1Z6L1 View 3D Structure Click here
A4F267 View 3D Structure Click here
B0R197 View 3D Structure Click here
B4FM49 View 3D Structure Click here
B4FX24 View 3D Structure Click here
B6TAU9 View 3D Structure Click here
B6TEP3 View 3D Structure Click here
C4IYM7 View 3D Structure Click here
C5NTE7 View 3D Structure Click here
C6KT11 View 3D Structure Click here
C6TAH8 View 3D Structure Click here
C6TGZ7 View 3D Structure Click here
C6TID5 View 3D Structure Click here
I1J462 View 3D Structure Click here
I1KQE2 View 3D Structure Click here
I1KXQ3 View 3D Structure Click here
I1L602 View 3D Structure Click here
I1LVS0 View 3D Structure Click here
I1LWI5 View 3D Structure Click here
I1MSR7 View 3D Structure Click here
I1N4A7 View 3D Structure Click here
I1N628 View 3D Structure Click here
K7KKS3 View 3D Structure Click here
K7KML2 View 3D Structure Click here
K7KVW5 View 3D Structure Click here
K7MKU5 View 3D Structure Click here
K7VNQ7 View 3D Structure Click here
O13656 View 3D Structure Click here
O96008 View 3D Structure Click here
P04840 View 3D Structure Click here
P21796 View 3D Structure Click here
P23644 View 3D Structure Click here
P40478 View 3D Structure Click here
P42057 View 3D Structure Click here
P45880 View 3D Structure Click here
P81155 View 3D Structure Click here
P83781 View 3D Structure Click here
Q01501 View 3D Structure Click here
Q0JJV1 View 3D Structure Click here
Q10M45 View 3D Structure Click here
Q10S27 View 3D Structure Click here
Q18090 View 3D Structure Click here
Q21752 View 3D Structure Click here
Q5AH14 View 3D Structure Click here
Q60930 View 3D Structure Click here
Q60931 View 3D Structure Click here
Q60932 View 3D Structure Click here
Q6K548 View 3D Structure Click here
Q6L5I5 View 3D Structure Click here
Q6NWC1 View 3D Structure Click here
Q6NWH3 View 3D Structure Click here
Q75Q40 View 3D Structure Click here
Q76P15 View 3D Structure Click here
Q7F4F8 View 3D Structure Click here
Q7T314 View 3D Structure Click here
Q7ZV39 View 3D Structure Click here
Q84P97 View 3D Structure Click here
Q8AWD0 View 3D Structure Click here
Q8ILE3 View 3D Structure Click here
Q94920 View 3D Structure Click here
Q969M1 View 3D Structure Click here
Q9CZR3 View 3D Structure Click here
Q9FHQ9 View 3D Structure Click here
Q9FJX3 View 3D Structure Click here
Q9FKM2 View 3D Structure Click here
Q9LHE5 View 3D Structure Click here
Q9M2W6 View 3D Structure Click here
Q9M2W6 View 3D Structure Click here
Q9P544 View 3D Structure Click here
Q9QYA2 View 3D Structure Click here
Q9R1Z0 View 3D Structure Click here
Q9SMX3 View 3D Structure Click here
Q9SPD7 View 3D Structure Click here
Q9SRH5 View 3D Structure Click here
Q9SX55 View 3D Structure Click here
Q9U4L6 View 3D Structure Click here
Q9VF44 View 3D Structure Click here
Q9VKP2 View 3D Structure Click here
Q9VKP3 View 3D Structure Click here
Q9VKP4 View 3D Structure Click here
Q9Y277 View 3D Structure Click here
Q9Z2L0 View 3D Structure Click here