Abstract
Bcl-2-related proteins are critical regulators of cell survival that are localized to the outer mitochondrial, outer nuclear and endoplasmic reticulum membranes1–4. Despite their physiological importance, the biochemical function of Bcl-2-related proteins has remained elusive. The three-dimensional structure of Bcl-xL, an inhibitor of apoptosis, was recently shown to be similar to the structures of the pore-forming domains of bacterial toxins5. A key feature of these pore-forming domains is the ability to form ion channels in biological membranes6,7. Here we demonstrate that Bcl-xL shares this functional feature. Like the bacterial toxins, Bcl-xL can insert into either synthetic lipid vesicles or planar lipid bilayers and form an ion-conducting channel. This channel is pH-sensitive and becomes cation-selective at physiological pH. The ion-conducting channel(s) formed by Bcl-xL display multiple conductance states that have identical ion selectivity. Together, these data suggest that Bcl-xL may maintain cell survival by regulating the permeability of the intracellular membranes to which it is distributed.
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References
White, E. Genes Dev. 10, 1–15 (1996).
Yang, E. & Korsmeyer, S. J. Blood 88, 386–401 (1996).
Lithgow, T., van Driel, R., Bertram, J. F. & Strasser, A. Cell Growth Differ. 5, 411–417 (1994).
Krajewski, S. et al. Cancer Res. 53, 4701–4714 (1993).
Muchmore, S. W. et al. Nature 381, 335–341 (1996).
London, E. Biochim. Biophys. Acta 1113, 25–51 (1992).
Cramer, W. A. et al. Annu. Rev. Biophys. Biomol. Struct. 24, 611–641 (1995).
Chen-Levy, Z. & Cleary, M. L. J. Biol. Chem. 265, 4929–4933 (1990).
Nguyen, M., Millar, D. G., Yong, V. W., Korsmeyer, S. J. & Shore, G. C. J. Biol. Chem. 268, 25265–2526 (1993).
Parker, M. W. & Pattus, F. Trends Biochem. Sci. 18, 391–395 (1993).
Choe, S. et al. Nature 357, 216–222 (1992).
Davidson, V. L., Heymann, J. B., Zhang, Y. L. & Cohen, F. S. J. Membr. Biol. 79, 105–118 (1984).
Zakharov, S. D., Heymann, J. B., Zhang, Y. L. & Cramer, W. A. Biophys. J. 70, 2774–2783 (1996).
Lam, M. et al. Proc. Natl Acad. Sci. USA 91, 6569–6573 (1994).
Zhu, W. et al. EMBO J. 15, 4130–4141 (1996).
Perez-Terzic, C., Pyle, J., Jaconi, M., Stehno-Bittel, L. & Clapham, D. E. Science 273, 1875–1877 (1996).
Mannella, C. A. Trends Biochem. Sci. 17, 315–320 (1992).
Zoratti, M. & Szabo, I. Biochim. Biophys. Acta 1241, 139–176 (1995).
Zamzami, N. et al. J. Exp. Med. 183, 1533–1544 (1996).
Liu, X., Kim, C. N., Yang, J., Jemmerson, R. & Wang, X. Cell 86, 147–157 (1996).
Martin, S. J. & Green, D. R. Cell 82, 349–352 (1995).
Slatin, S. L., Abrams, C. K. & English, L. Biochem. Biophys. Res. Commun. 169, 765–772 (1990).
Hoch, D. H. et al. Proc. Natl Acad. Sci. USA 82, 1692–1696 (1985).
Raymond, L., Slatin, S. L. & Finkelstein, A. J. Membr. Biol. 84, 173–181 (1985).
Wistow, G. Trends Biochem. Sci. 18, 301–306 (1993).
Tomarev, S. I. & Piatigorsky, J. Eur. J. Biochem. 235, 449–465 (1996).
Peterson, A. A. & Cramer, W. A. J. Membr. Biol. 99, 197–204 (1987).
Cramer, W. A. & Knaff, D. B. Energy Transduction in Biological Membranes, a Textbook of Bioenergetics (Springer, New York, 1990).
Györke, S. & Fill, M. Science 260, 807–809 (1993).
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Minn, A., Vélez, P., Schendel, S. et al. Bcl-xL forms an ion channel in synthetic lipid membranes. Nature 385, 353–357 (1997). https://doi.org/10.1038/385353a0
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DOI: https://doi.org/10.1038/385353a0
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