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Bcl-xL forms an ion channel in synthetic lipid membranes

Nature volume 385, pages 353–357 (1997)Cite this article

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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Authors and Affiliations

  1. Gwen Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, Illinois, 60637, USA

    Andy J. Minn & Craig B. Thompson

  2. Committee on Immunology, The University of Chicago, Chicago, Illinois, 60637, USA

    Andy J. Minn & Craig B. Thompson

  3. Howard Hughes Medical Institute, Department of Medicine, and Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, Illinois, 60637, USA

    Craig B. Thompson

  4. Department of Physiology, Cardiovascular Institute, Loyola University of Chicago Stritch School of Medicine, Maywood, Illinois, 60153, USA

    Patricio Vélez & Michael Fill

  5. Department of Biological Sciences, Purdue University, West Lafayette, Indiana, 47907, USA

    Sharon L. Schendel

  6. NMR Resarch, Abbott Laboratories, Abbott Park, Illinois, 60064, USA

    Heng Liang & Stephen W. Fesik

  7. Protein Crystallography, Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, Illinois, 60064, USA

    Steven W. Muchmore

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  1. Andy J. Minn
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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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