LifeTein synthesized the C subunit of the ATP synthase. The c subunit is a highly hydrophobic peptide of 75 residues. This is a transmembrane α-helical “hairpin” localized in the mitochondrial inner membrane where it assembles into oligomers of 8–16 units depending on the species.
The long peptide of the C subunit spontaneously folds into a β‑sheet conformation. This was confirmed by the peptide’s far-UV circular dichroism (CD) spectrum. The c subunit in β-sheet conformation could form aggregates. The formation of cross-β aggregates was monitored using the amyloid-binding dye Tiofavin T (TT). It was found that a critical role for Ca2+ in the folding and self-assembly of c subunits into oligomers rather than fibrils.
The amyloidogenic peptides can form ion channels in lipid bilayers. The human unmodified synthetic c subunit is an amyloidogenic peptide and its oligomers
are capable of forming ion-conducting pores in planar lipid bilayers. Similarly, amyloid and synuclein in their oligomeric conformations can form ion channels in planar lipid bilayers with lower conductances compared to the canonical PTP. These toxic forms of misfolded c subunit might play a significant role in cell pathophysiology.