Native Glucagon Amyloids Catalyze Key Metabolic Reactions

Research output: Contribution to journalArticlepeer-review

Abstract

Glucagon is a prominent peptide hormone, playing central roles in the regulation of glucose blood-level and lipid metabolism. Formation of glucagon amyloid fibrils has been previously reported, although no biological functions of such fibrils are known. Here, we demonstrate that glucagon amyloid fibrils catalyze biologically important reactions, including esterolysis, lipid hydrolysis, and dephosphorylation. In particular, we found that glucagon fibrils catalyze dephosphorylation of adenosine triphosphate (ATP), a core metabolic reaction in cell biology. Comparative analysis of several glucagon variants allowed mapping the catalytic activity to an enzymatic pocket-like triad formed at the glucagon fibril surface, comprising the histidyl-serine domain at the N-terminus of the peptide. This study may point to previously unknown physiological roles and pathological consequences of glucagon fibrillation and supports the hypothesis that catalytic activities of native amyloid fibrils play functional roles in human physiology and disease.

Original languageEnglish
Pages (from-to)12889-12899
Number of pages11
JournalACS Nano
Volume16
Issue number8
DOIs
StatePublished - 23 Aug 2022

Keywords

  • ATP dephosphorylation
  • catalytic amyloids
  • ester-hydrolysis
  • glucagon
  • lipid hydrolysis

ASJC Scopus subject areas

  • Materials Science (all)
  • Engineering (all)
  • Physics and Astronomy (all)

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