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

ATP acts as a biological hydrotrope preventing protein aggregation. Here, we report a novel chimeric peptide, ACC(1-13)K(8), 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 (K-8). Fibrillization requires binding 2 ATP molecules per ACC(1-13)K(8) 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(1-13)K(8) not observed for ACC(1-13) and K-8 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.

Automated summary

The novel chimeric peptide ACC(1-13)K(8) has the ability to bind and incorporate ATP while self-assembling into amyloid fibrils. The incorporation of ATP is a new property of ACC(1-13)K(8) not seen in the separate ACC(1-13) and K-8 segments. This suggests a more nuanced role for ATP in protein misfolding than previously assumed.