pH-dependent self-assembly of human neuropeptide hormone GnRH into functional amyloid nanofibrils and hexagonal phases

Gonadotropin-releasing hormone (GnRH) is a short human neuropeptide involved in the regulation of sex hormones. We report that GnRH self-assembles into reversible β-sheet-based nanofibrils, with pH-dependent kinetics. At high concentrations, these nanostructures form arrays arranged in liquid crystalline hexagonal phases. Histidine deprotonation with increasing pH can mediate the formation of β-sheet-based precipitates. Our results are relevant to functional amyloids in general, to the intracellular storage process of GnRH within secretory granules, and to peptide hormone drug delivery.