Molecular Interpretation of ACTH-[beta]-Endorphin Coaggregation: Relevance to Secretory Granule Biogenesis

Peptide/protein hormones could be stored as non-toxic amyloid-like structures in pituitary secretory granules. ACTH and [beta]-endorphin are two of the important peptide hormones that get co-stored in the pituitary secretory granules. Here, we study molecular interactions between ACTH and [beta]-endorphin and their colocalization in the form of amyloid aggregates. Although ACTH is known to be a part of ACTH-[beta]-endorphin aggregate, ACTH alone cannot aggregate into amyloid under various plausible conditions. Using all atom molecular dynamics simulation we investigate the early molecular interaction events in the ACTH-[beta]-endorphin system, [beta]-endorphin-only system and ACTH-only system. We find that [beta]-endorphin and ACTH formed an interacting unit, whereas negligible interactions were observed between ACTH molecules in ACTH-only system. Our data suggest that ACTH is not only involved in interaction with [beta]-endorphin but also enhances the stability of mixed oligomers of the entire system.