Molecular interpretation of ACTH-?-endorphin coaggregation: relevance to secretory granule biogenesis.

ABSTRACT: Peptide/protein hormones could be stored as non-toxic amyloid-like structures in pituitary secretory granules. ACTH and ?-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 ?-endorphin and their colocalization in the form of amyloid aggregates. Although ACTH is known to be a part of ACTH-?-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-?-endorphin system, ?-endorphin-only system and ACTH-only system. We find that ?-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 ?-endorphin but also enhances the stability of mixed oligomers of the entire system.

SUBMITTER: Ranganathan S 

PROVIDER: S-EPMC3293876 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature