Analysis of the Role of the Conserved Disulfide in Amyloid Formation by Human Islet Amyloid Polypeptide in Homogeneous and Heterogeneous Environments.

ABSTRACT: Human islet amyloid polypeptide (hIAPP) is a hormone secreted from β-cells in the Islets of Langerhans in response to the same stimuli that lead to insulin secretion. hIAPP plays an adaptive role in glucose homeostasis but misfolds to form insoluble, fibrillar aggregates in type II diabetes that are associated with the disease. Along the misfolding pathway, hIAPP forms species that are toxic to β-cells, resulting in reduced β-cell mass. hIAPP contains a strictly conserved disulfide bond between residues 2 and 7, which forms a small loop at the N-terminus of the molecule. The loop is located outside of the cross β-core in all models of the hIAPP amyloid fibrils. Mutations in this region are rare, and the disulfide loop plays a role in receptor binding; however, the contribution of this regi

SUBMITTER: Ridgway Z 

PROVIDER: S-EPMC6009826 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature