Selective and stoichiometric incorporation of ATP by self-assembling amyloid fibrils

Abstract

ATP acts as a biological hydrotrope preventing protein aggregation. Here, we report a novel chimeric peptide, ACC_1–13K₈, with an unusual capacity to bind and incorporate ATP while self-assembling into amyloid fibrils. The amino acid sequence combines a highly amyloidogenic segment of insulin's A-chain (ACC_1–13) and octalysine (K₈). Fibrillization requires binding 2 ATP molecules per ACC_1–13K₈ monomer and is not triggered by adenosine di- and monophosphates (ADP, AMP). Infrared and CD spectra and AFM-based morphological analysis reveal tight and orderly entrapment of ATP within superstructural hybrid peptide–ATP fibrils. The incorporation of ATP is an emergent property of ACC_1–13K₈ not observed for ACC_1–13 and K₈ segments separately. We demonstrate how new functionalities (e.g. ATP storage) emerge from synergistic coupling of amyloidogenic segments with non-amyloidogenic peptide ligands, and suggest that ATP's role in protein misfolding is more nuanced than previously assumed.