A Free Energy Barrier Caused by the Refolding of an Oligomeric Intermediate Controls the Lag Time of Amyloid Formation by hIAPP.

ABSTRACT: Transiently populated oligomers formed en route to amyloid fibrils may constitute the most toxic aggregates associated with many amyloid-associated diseases. Most nucleation theories used to describe amyloid aggregation predict low oligomer concentrations and do not take into account free energy costs that may be associated with structural rearrangements between the oligomer and fiber states. We have used isotope labeling and two-dimensional infrared spectroscopy to spectrally resolve an oligomeric intermediate during the aggregation of the human islet amyloid protein (hIAPP or amylin), the protein associated with type II diabetes. A structural rearrangement includes the F₂₃G₂₄A₂₅I₂₆L₂₇ region of hIAPP, which starts from a random coil

SUBMITTER: Serrano AL 

PROVIDER: S-EPMC5859135 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature