Structure-based Analysis of VDAC1 Protein
Open accessAbstract
The outer mitochondrial membrane protein, the voltage-dependent anion channel (VDAC), is increasingly implicated in the control of apoptosis. Oligomeric assembly of VDAC1 was shown to be coupled to apoptosis induction, with oligomerization increasing substantially upon apoptosis induction and inhibited by apoptosis blockers. In this study, structure- and computation-based selection of the predicated VDAC1 dimerization site, in combination with site-directed mutagenesis, cysteine replacement, and chemical cross-linking, were employed to identify contact sites between VDAC1 molecules in dimers and higher oligomers. The predicted weakly stable β-strands were experimentally found to represent the interfaces between VDAC1 monomers composing the oligomer. Replacing hydrophobic amino acids with charged residues in β-strands 1, 2, and 19 interfered with VDAC1 oligomerization. The proximity of β-strands 1, 2, and 19 within the VDAC1 dimer and the existence of other association sites involving β-strand 16 were confirmed when a cysteine was introduced at defined positions in cysteineless VDAC1 mutants, together with the use of cysteine-specific cross-linker bis(maleimido)ethane. Moreover, the results suggest that VDAC1 also exists as a dimer that upon apoptosis induction undergoes conformational changes and that its oligomerization proceeds through a series of interactions involving two distinct interfaces. Dissection of VDAC1 dimerization/oligomerization as presented here provides structural insight into the oligomeric status of cellular VDAC1 under physiological and apoptotic conditions.
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The N-terminal domain of VDAC1 interacts with several Bcl-2 family proteins that regulate apoptosis and is involved in gating the channel.
“The N-terminal domain of VDAC1 interacts with several Bcl-2 family proteins that regulate apoptosis and is involved in gating the channel [96,97,98,99,100,101].”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [96]
The introductory passage labeled Abstract says VDAC1 interacts with pro- and anti-apoptotic proteins and places its N-terminal helix within the pore. It does not say that the N-terminal domain specifically interacts with several Bcl-2 family proteins or that it gates the channel; the paper’s reported findings instead concern VDAC1 oligomer contact sites. (LLM, conf=0.76)
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Cites
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
LAEMMLI, U. K. (1970) · Nature · doi:10.1038/227680a0 · Cited by 249,961 · see citing works
VDAC, a multi-functional mitochondrial protein regulating cell life and death
Shoshan‐Barmatz, V., Pinto, V. D., Zweckstetter, M., Raviv, Z., Keinan, N., & Arbel, N. (2010) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2010.03.002 · Cited by 792 · see citing works
Self-citationSiderophore-Mediated Iron Transport: Crystal Structure of FhuA with Bound Lipopolysaccharide
Ferguson, A. D., Hofmann, E., Coulton, J. W., Diederichs, K., & Welte, W. (1998) · Science · doi:10.1126/science.282.5397.2215 · Cited by 787 · see citing works
Solution structure of the integral human membrane protein VDAC-1 in detergent micelles
Hiller, S., Garces, R. G., Malia, T. J., Orekhov, V. Y., Colombini, M., & Wagner, G. (2008) · Science · doi:10.1126/science.1161302 · Cited by 667 · see citing works
Structure of the human voltage-dependent anion channel
Bayrhuber, M., Meins, T., Habeck, M., Becker, S., Giller, K., Villinger, S., Vonrhein, C., Griesinger, C., Zweckstetter, M., & Zeth, K. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808115105 · Cited by 588 · see citing works
Ujwal, R., Cascio, D., Colletier, J., Faham, S., Zhang, J., Toro, L., Ping, P., & Abramson, J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809634105 · Cited by 546 · see citing works
VDAC: The channel at the interface between mitochondria and the cytosol
Colombini, M. (2003) · Molecular and Cellular Biochemistry · doi:10.1023/b:mcbi.0000009862.17396.8d · Cited by 500 · see citing works
Multiple pathways of cytochrome c release from mitochondria in apoptosis
Gogvadze, V. G., Orrenius, S., & Zhivotovsky, B. (2006) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2006.03.016 · Cited by 466 · see citing works
Voltage-dependent anion channel (VDAC) as mitochondrial governator—Thinking outside the box
Lemasters, J. J., & Holmuhamedov, E. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2005.10.006 · Cited by 437 · see citing works
Shimizu, S., Ide, T., Yanagida, T., & Tsujimoto, Y. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.16.12321 · Cited by 338 · see citing works
Shoshan‐Barmatz, V., Israelson, A., Brdiczka, D. G., & Sheu, S. (2006) · Current Pharmaceutical Design · doi:10.2174/138161206777585111 · Cited by 307 · see citing works
Self-citationThe voltage-dependent anion channel-1 modulates apoptotic cell death
Zaid, H., Abu‐Hamad, S., Israelson, A., Nathan, I., & Shoshan‐Barmatz, V. (2005) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401599 · Cited by 299 · see citing works
Self-citationKeinan, N., Tyomkin, D., & Shoshan‐Barmatz, V. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.00165-10 · Cited by 269 · see citing works
Self-citationThe voltage-dependent anion channel: an essential player in apoptosis
Tsujimoto, Y., & Shimizu, S. (2002) · Biochimie · doi:10.1016/s0300-9084(02)01370-6 · Cited by 251 · see citing works
The expression level of the voltage-dependent anion channel controls life and death of the cell
Abu‐Hamad, S., Sivan, S., & Shoshan‐Barmatz, V. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600103103 · Cited by 240 · see citing works
Self-citationMolassiotis, A., & Cubbin, D. (2004) · European Journal of Oncology Nursing · doi:10.1016/s1462-3889(03)00054-1 · Cited by 230 · see citing works
Abu-Hamad, S., Arbel, N., Calo, D., Arzoine, L., Israelson, A., Keinan, N., Ben-Romano, R., Friedman, O., & Shoshan-Barmatz, V. (2009) · Journal of Cell Science · doi:10.1242/jcs.040188 · Cited by 226 · see citing works
Self-citationOligomeric states of the voltage-dependent anion channel and cytochrome c release from mitochondria
Zalk, R., Israelson, A., GARTY, E. S., Azoulay‐Zohar, H., & Shoshan‐Barmatz, V. (2005) · Biochemical Journal · doi:10.1042/bj20041356 · Cited by 222 · see citing works
Self-citationThe Supramolecular Assemblies of Voltage-dependent Anion Channels in the Native Membrane
Hoogenboom, B. W., Suda, K., Engel, A. H., & Fotiadis, D. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.04.073 · Cited by 174 · see citing works
Malia, T., & Wagner, G. (2006) · Biochemistry · doi:10.1021/bi061577h · Cited by 164 · see citing works
The voltage-dependent anion channel
Shoshan-Barmatz, V., & Gincel, D. (2007) · Cell Biochemistry and Biophysics · doi:10.1385/cbb:39:3:279 · Cited by 158 · see citing works
Self-citationSupramolecular Assembly of VDAC in Native Mitochondrial Outer Membranes
Gonçalves, R. P., Buzhynskyy, N., Prima, V., Sturgis, J. N., & Simon Scheuring, A. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.03.063 · Cited by 157 · see citing works
Shoshan‐Barmatz, V., Keinan, N., Abu‐Hamad, S., Tyomkin, D., & Aram, L. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.03.003 · Cited by 147 · see citing works
Self-citationKey regions of VDAC1 functioning in apoptosis induction and regulation by hexokinase
Shoshan‐Barmatz, V., Zakar, M., Rosenthal, K., & Abu‐Hamad, S. (2008) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2008.11.009 · Cited by 139 · see citing works
Self-citationPedersen, P. L. (2008) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-008-9165-7 · Cited by 136 · see citing works
Pinto, V. D., Prezioso, G., Thinnes, F., Link, T. A., & Palmieri, F. (1991) · Biochemistry · doi:10.1021/bi00106a017 · Cited by 128 · see citing works
Mapping of residues forming the voltage sensor of the voltage-dependent anion-selective channel.
Thomas, L., Blachly‐Dyson, E., Colombini, M., & Forte, M. A. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.12.5446 · Cited by 118 · see citing works
Walther, D. M., Papić, D., Bos, M. P., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0807830106 · Cited by 117 · see citing works
The published 3D structure of the VDAC channel: native or not?
Colombini, M. (2009) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2009.05.001 · Cited by 111 · see citing works
Saks, V. A., Guzun, R., Timohhina, N., Tepp, K., Varikmaa, M., Monge, C., Béraud, N., Käämbre, T., Kuznetsov, A. V., Kadaja, L., et al. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.01.011 · Cited by 108 · see citing works
Guo, X. W., Smith, P. R., Cognon, B., D'Arcangelis, D., Dolginova, E. A., & Mannella, C. A. (1995) · Journal of Structural Biology · doi:10.1006/jsbi.1995.1004 · Cited by 97 · see citing works
Lipid-binding surfaces of membrane proteins: Evidence from evolutionary and structural analysis
Adamian, L., Naveed, H., & Liang, J. (2010) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2010.12.008 · Cited by 72 · see citing works
Self-citationStanley, S., Dias, J. A., D'Arcangelis, D., & Mannella, C. A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.28.16694 · Cited by 69 · see citing works
Naveed, H., Jackups, R., & Liang, J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0902169106 · Cited by 64 · see citing works
Self-citationGranville, D. J., & Gottlieb, R. A. (2003) · Current Medicinal Chemistry · doi:10.2174/0929867033457214 · Cited by 58 · see citing works
Mannella, C. A., Colombini, M., & Frank, J. (1983) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.80.8.2243 · Cited by 56 · see citing works
Ujwal, R., Cascio, D., Chaptal, V., Ping, P., & Abramson, J. (2009) · Channels · doi:10.4161/chan.3.3.9196 · Cited by 54 · see citing works
Walther, D. M., Bos, M. P., Rapaport, D., & Tommassen, J. (2009) · Molecular Biology and Evolution · doi:10.1093/molbev/msp294 · Cited by 49 · see citing works
VDAC1 cysteine residues: topology and function in channel activity and apoptosis
Aram, L., Geula, S., Arbel, N., & Shoshan‐Barmatz, V. (2010) · Biochemical Journal · doi:10.1042/bj20091690 · Cited by 47 · see citing works
Self-citationJimenez‐Morales, D., & Liang, J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026400 · Cited by 21 · see citing works
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Flagged first, then by citations
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VDAC1, mitochondrial dysfunction, and Alzheimer’s disease
Shoshan-Barmatz, V., Nahon-Crystal, E., Shteinfer-Kuzmine, A., & Gupta, R. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.03.010 · Cited by 286 · see citing works
Self-citationVDAC1 at the crossroads of cell metabolism, apoptosis and cell stress
Shoshan-Barmatz, V., N. Maldonado, E., & Krelin, Y. (2017) · Cell Stress · doi:10.15698/cst2017.10.104 · Cited by 170 · see citing works
Self-citationGeula, S., Ben-Hail, D., & Shoshan-Barmatz, V. (2012) · Biochemical Journal · doi:10.1042/bj20112079 · Cited by 105 · see citing works
Self-citationMitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease
Butterfield, D. A., & Boyd-Kimball, D. (2020) · Antioxidants · doi:10.3390/antiox9090818 · Cited by 85 · see citing works
VDAC1-interacting anion transport inhibitors inhibit VDAC1 oligomerization and apoptosis
Ben-Hail, D., & Shoshan-Barmatz, V. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2016.04.002 · Cited by 80 · see citing works
Self-citationAssociation of Aβ with ceramide-enriched astrosomes mediates Aβ neurotoxicity
Elsherbini, A., Kirov, A. S., Dinkins, M. B., Wang, G., Qin, H., Zhu, Z., Tripathi, P., Crivelli, S. M., & Bieberich, E. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-00931-8 · Cited by 72 · see citing works
- Authors
- Geula, S., Naveed, H., Liang, J., & Shoshan-Barmatz, V.
- Affiliations
- Ben-Gurion University of the Negev (IL)
- University of Illinois Chicago (US)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 287
- Issue
- 3
- Pages
- 2179-2190
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3265896
- OpenAlex
- W1991392283
- Cited by
- 97
- References
- 40
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 5 · 2023: 6 · 2022: 4 · 2021: 8 · 2020: 10 · 2019: 2 · 2018: 5 · 2017: 7 · 2016: 8 · 2015: 5 · 2014: 9 · 2013: 6 · 2012: 4
- FWCI
- 2.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- 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
- Keywords
- VDAC1, voltage-dependent anion channel, mitochondrial outer membrane, apoptosis, protein oligomerization, protein dimerization, protein-protein interfaces, conformational change, site-directed mutagenesis, crosslinking
- MeSH terms
- Animals, Humans, Structure-Activity Relationship, Apoptosis, Protein Structure, Secondary, Protein Structure, Quaternary, Voltage-Dependent Anion Channel 1, Mice, Rats, Protein Multimerization, HEK293 Cells
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