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Membrane‐dependent amyloid aggregation of human BAX α9 (173–192)
Author(s) -
Price David A.,
Hill Tayler D.,
Hutson Kaitlyn A.,
Rightnowar Blaze W.,
Moran Sean D.
Publication year - 2021
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.4053
Subject(s) - thioflavin , biophysics , peptide , vesicle , membrane , chemistry , amyloid (mycology) , apoptosis , helix (gastropod) , peptide sequence , membrane biology , transmembrane domain , circular dichroism , transmembrane protein , biochemistry , biology , alzheimer's disease , medicine , inorganic chemistry , ecology , receptor , disease , pathology , snail , gene
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.