Polymorphic Amyloid Nanostructures of Hormone Peptides Involving Glucose Homeostasis

A large group of hormones are stored as amyloid fibrils in acidic secretion vesicles before they are released into the bloodstream and readopt their functional state. This phenomenon is studied in relation to the glucagon family peptides, which involve conserved receptor binding segments with dual functionality: amyloid-prone regions involved in pH-dependent conversion from secretory amyloid fibrils to the functional folded form. The researchers investigate this topic using various techniques such as CD, FTIR, ThT assays, and AFM to understand the role of glutamate/aspartate residues in initiating switching between amyloid and monomeric forms of the hormones. They also determine nine polymorphic crystal structures of the major aggregation-prone region (APR) segments of glucagon-like peptides 1 and 2, exendin, and its derivatives.