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Updated: Aug 21, 2026
Examining BCL-2 Family Function with Large Unilamellar Vesicles
Published on: October 5, 2012
Conformational changes in BID, a pro-apoptotic BCL-2 family member, upon membrane binding. A site-directed spin
Kyoung Joon Oh1, Scott Barbuto, Natalie Meyer
1Howard Hughes Medical Institute, the Department of Pathology and Medicine, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Abstract:
The BCL-2 family proteins constitute a critical control point in apoptosis. BCL-2 family proteins display structural homology to channel-forming bacterial toxins, such as colicins, transmembrane domain of diphtheria toxin, and the N-terminal domain of delta-endotoxin. By analogy, it has been hypothesized the BCL-2 family proteins would unfold and insert into the lipid bilayer upon membrane association. We applied the site-directed spin labeling method of electron paramagnetic resonance spectroscopy to the pro-apoptotic member BID. Here we show that helices 6-8 maintain an alpha-helical conformation in membranes with a lipid composition resembling mitochondrial outer membrane contact sites. However, unlike colicins and the transmembrane domain of diphtheria toxin, these helices of BID are bound to the lipid bilayer without adopting a transmembrane orientation. Our study presents a more detailed model for the reorganization of the structure of tBID on membranes.
Insights
The pro-apoptotic protein BID
Area of Science:
- Molecular Biology
- Biophysics
- Cell Biology
Background:
- The BCL-2 family regulates apoptosis.
- BCL-2 proteins share structural similarities with bacterial toxins.
- Previous hypotheses suggested BCL-2 proteins insert into lipid bilayers.
Purpose of the Study:
- To investigate the membrane interaction of the pro-apoptotic protein BID.
- To elucidate the structural changes of BID upon membrane association.
Main Methods:
- Site-directed spin labeling.
- Electron paramagnetic resonance (EPR) spectroscopy.
- Lipid bilayers mimicking mitochondrial outer membrane contact sites.
Main Results:
- Helices 6-8 of BID maintain alpha-helical structure in membranes.
- These helices bind to the lipid bilayer.
- BID helices do not adopt a transmembrane orientation, unlike hypothesized bacterial toxins.
Conclusions:
- The study refines the model of tBID reorganization on membranes.
- BID's membrane interaction differs from channel-forming bacterial toxins.
- This provides new insights into apoptosis regulation at the molecular level.
