Related Experiment Video
Updated: Nov 16, 2025
Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
Published on: September 28, 2019
Membrane-dependent amyloid aggregation of human BAX α9 (173-192)
David A Price1, Tayler D Hill1, Kaitlyn A Hutson1
1Department of Chemistry and Biochemistry, Southern Illinois University Carbondale, Carbondale, Illinois, USA.
Abstract:
Mitochondrial outer membrane permeabilization, which is a critical step in apoptosis, is initiated upon transmembrane insertion of the C-terminal α-helix (α9) of the proapoptotic Bcl-2 family protein BAX. The isolated α9 fragment (residues 173-192) is also competent to disrupt model membranes, and the structures of its membrane-associated oligomers are of interest in understanding the potential roles of this sequence in apoptosis. Here, we used ultrafast two-dimensional infrared (2D IR) spectroscopy, thioflavin T binding, and transmission electron microscopy to show that the synthetic BAX α9 peptide (α9p) forms amyloid aggregates in aqueous environments and on the surfaces of anionic small unilamellar vesicles. Its inherent amyloidogenicity was predicted by sequence analysis, and 2D IR spectra reveal that vesicles modulate the β-sheet structures of insoluble aggregates, motivating further examination of the formation or suppression of BAX amyloids in apoptosis.
Insights
The BAX alpha9 peptide forms amyloid aggregates, influencing apoptosis. Vesicles alter these structures, suggesting a role for BAX amyloids in programmed cell death.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Mitochondrial outer membrane permeabilization is key in apoptosis.
- The BAX protein's C-terminal alpha-helix (α9) initiates this process.
- Understanding BAX α9's membrane interactions is crucial for apoptosis research.
Purpose of the Study:
- To investigate the aggregation behavior of the synthetic BAX α9 peptide (α9p).
- To characterize the structures of BAX α9p aggregates in aqueous and membrane environments.
- To explore the implications of BAX α9 aggregation in apoptosis.
Main Methods:
- Ultrafast two-dimensional infrared (2D IR) spectroscopy.
- Thioflavin T binding assays.
- Transmission electron microscopy (TEM).
- Sequence analysis for amyloidogenicity prediction.
Main Results:
- The synthetic BAX α9 peptide (α9p) forms amyloid aggregates in solution and on anionic vesicles.
- 2D IR spectroscopy revealed that vesicles modulate the β-sheet structures of these aggregates.
- Amyloid formation propensity was predicted by sequence analysis.
Conclusions:
- The BAX α9 peptide exhibits inherent amyloidogenicity.
- Membrane interactions can alter the structure of BAX α9 amyloid aggregates.
- Further research is needed to understand the role of BAX amyloids in apoptosis regulation.
Related Concept Videos
03:03Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
03:03Amyloid Fibrils