Structural Polymorphs Suggest Competing Pathways for the Formation of Amyloid Fibrils That Diverge from a Common Intermediate Species.

ABSTRACT: It is now recognized that many amyloid-forming proteins can associate into multiple fibril structures. Here, we use two-dimensional infrared spectroscopy to study two fibril polymorphs formed by human islet amyloid polypeptide (hIAPP or amylin), which is associated with type 2 diabetes. The polymorphs exhibit different degrees of structural organization near the loop region of hIAPP fibrils. The relative populations of these polymorphs are systematically altered by the presence of macrocyclic peptides which template β-sheet formation at specific sections of the hIAPP sequence. These experiments are consistent with polymorphs that result from competing pathways for fibril formation and that the macrocycles bias hIAPP aggregation toward one pathway or the other. Another macrocyclic peptide t

SUBMITTER: Buchanan LE 

PROVIDER: S-EPMC6368979 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature