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Logo of jbcThe Journal of Biological Chemistry
J Biol Chem. 2015 March 6; 290(10): 5959.
PMCID: PMC4358233

Insight into Fibrillation Kinetics of Insulin Fragments♦

Highly Amyloidogenic Two-chain Peptide Fragments Are Released upon Partial Digestion of Insulin with Pepsin

♦ See referenced article, J. Biol. Chem. 2015, 290, 5947–5958

Proteolysis is an essential step in amyloidogenic fibril formation in physiological and pathophysiological conditions. Proteolysis of amyloidogenic proteins in vivo is likely to be incomplete, and the kinetics of fibril formation under conditions of partial proteolysis are not well understood. In this Paper of the Week, Wojciech Dzwolak's group at the Polish Academy of Sciences and the University of Warsaw explored the kinetics of amyloid fibrillation of insulin after partial proteolytic digestion. Partial pepsin digestion of bovine insulin resulted in an unexpected “explosive” formation of amyloidogenic fibrils. The authors identified the highly amyloidogenic insulin fragment and demonstrated that the disulfide bonds of the fragment are essential for amyloidogenesis. The authors say, “Our results point to a significant amyloidogenic potential of insulin molecule being ‘unleashed’ upon cutting open its central topological loop.” Understanding amyloid fibrillation after limited proteolysis, which may mimic physiological conditions, is an important step in deciphering this process in vivo.

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Schematic structure of amyloid-building fragments from partial pepsin digestion of insulin.

Articles from The Journal of Biological Chemistry are provided here courtesy of American Society for Biochemistry and Molecular Biology