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, ACC1-13K8, 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 (ACC1-13) and octalysine (K8). Fibrillization requires binding 2 ATP molecules per ACC1-13K8 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 ACC1-13K8 not observed for ACC1-13 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.

• Publication year

  2021

• Venue

  Journal of materials chemistry. B

• Publication date

  2021-07-06

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.33774/chemrxiv-2021-94z8zPMID 34622264
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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