Bcl-x(L) forms an ion channel in synthetic lipid membranes.

Minn AJ, VĂ©lez P, Schendel SL, Liang H, Muchmore SW, Fesik SW, Fill M, Thompson CB
Nature. 1997 385 (6614): 353-7

PMID: 9002522 · DOI:10.1038/385353a0

Bcl-2-related proteins are critical regulators of cell survival that are localized to the outer mitochondrial, outer nuclear and endoplasmic reticulum membranes. 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 toxins. A key feature of these pore-forming domains is the ability to form ion channels in biological membranes. 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.

MeSH Terms (15)

bcl-X Protein Cations Cell Membrane Permeability Electrochemistry Escherichia coli Humans Hydrogen-Ion Concentration Ion Channel Gating Ion Channels Kinetics Lipid Bilayers Protein Conformation Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 Recombinant Proteins

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