Islet amyloid formation by islet amyloid polypeptide (IAPP, also known as amylin) is a common feature of type 2 diabetes and contributes to the loss of beta cells during the disease. Islet amyloid also plays a role in the failure of islet transplants. The mechanism of amyloid formation by IAPP is not completely understood, but aromatic-aromatic, aromatic-hydrophobic, and aromatic- histidine interactions have been proposed to play a critical role. We critically examined the role that the aromatic residues and the single His residue of IAPP play in amyloid formation. A set of single aromatic to Leu mutants were studied, as were all possible double aromatic to Leu mutants and a triple Leu mutant and a set of His mutants. None of the aromatic residues were required for amyloid formation, although aromatic mutations did alter the rate of amyloid formation. We also used these mutants to determine the potential binding sites of the IAPP amyloid inhibitor resveratrol.

Analysis of the role of aromatic interactions in amyloid formation by islet amyloid polypeptide

245th National Meeting (2013)

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