Conformational Dynamics of the Human Islet Amyloid Polypeptide in a Membrane Environment: Toward the Aggregation Prone Form.

ABSTRACT: Human islet amyloid polypeptide (hIAPP) is a 37-residue peptide hormone, which upon misfolding changes from the physiologically active monomer into pathological amyloid fibril aggregates in the pancreas of type 2 diabetes mellitus patients. During this process, the insulin-producing pancreatic β-cells are damaged; however, the underlying mechanism of this mode of cytotoxicity remains elusive. It is known that anionic lipids accelerate amyloid fibril formation, implicating the importance of the cellular membrane in the process, and that a pH close to the level in the β-cell secretory granules (pH 5.5) inhibits amyloid fibril formation. Using all-atom molecular dynamics simulations, we have investigated the membrane-associated monomer state of α-helical hIAPP, analyzed specific interactions

SUBMITTER: Skeby KK 

PROVIDER: S-EPMC5733697 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature