Structural similarities and differences between amyloidogenic and non-amyloidogenic islet amyloid polypeptide (IAPP) sequences and implications for the dual physiological and pathological activities of these peptides.

ABSTRACT: IAPP, a 37 amino-acid peptide hormone belonging to the calcitonin family, is an intrinsically disordered protein that is coexpressed and cosecreted along with insulin by pancreatic islet β-cells in response to meals. IAPP plays a physiological role in glucose regulation; however, in certain species, IAPP can aggregate and this process is linked to β-cell death and Type II Diabetes. Using replica exchange molecular dynamics with extensive sampling (16 replicas per sequence and 600 ns per replica), we investigate the structure of the monomeric state of two species of aggregating peptides (human and cat IAPP) and two species of non-aggregating peptides (pig and rat IAPP). Our simulations reveal that the pig and rat conformations are very similar, and consist of helix-coil and helix-hairpin co

SUBMITTER: Wu C 

PROVIDER: S-EPMC3757079 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature