TI  - <prot>Bcl-x(L)</prot> forms an ion channel in synthetic lipid membranes.
PG  - 353-7
AB  - <prot>Bcl-2</prot>-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 <prot>Bcl-2</prot>-related proteins has remained elusive. The
      three-dimensional structure of <prot>Bcl-xL</prot>, 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 <prot>Bcl-xL</prot> shares this functional feature. Like the bacterial toxins,
        <prot>Bcl-xL</prot>   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 <prot>Bcl-xL</prot> display multiple conductance states that have
      identical ion selectivity. Together, these data suggest that <prot>Bcl-xL</prot> may
      maintain cell survival by regulating the permeability of the intracellular
      membranes to which it is distributed.
AD  - Gwen Knapp Center for Lupus and Immunology Research, The University of
