Human islet amyloid polypeptide (hIAPP), generally known as Amylin, is co-secreted with insulin and it helps control blood glucose levels. However, upon aggregation it becomes harmful to pancreatic islet β-cells and it is widely found in fibril form in patients suffering from type 2 diabetes. The prevalence of diabetes is species-dependent: humans and cats are afflicted, whereas rats and pigs are not. We build several fibril models based on solid-state NMR data of hIAPP and performed single-point mutations from hIAPP to other species. Our computational study investigates the influence of different conformations and sequences on the fibril dynamics. Our results corroborate the experimental data on fibril formation in different species, which may motivate future experimental studies on amyloid aggregation-inhibiting drug design.

Mutations tuning the structure and dynamics of amylin fibrils

253rd National Meeting (2017)

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