title: Molecular interpretation of ACTH-β-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 β-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 β-endorphin and their colocalization in the form of amyloid aggregates. Although ACTH is known to be a part of ACTH-β-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-β-endorphin system, β-endorphin-only system and ACTH-only system. We find that β-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 β-endorphin but also enhances the stability of mixed oligomers of the entire system.
authors.affiliation: Department of Biosciences and Bioengineering, Wadhwani Research Centre for Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India.
authors.forename: Srivastav
authors.initials: S
authors.lastname: Ranganathan
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Singh
authors.forename: Uday
authors.initials: U
authors.lastname: Singh
authors.forename: Praful S
authors.initials: PS
authors.lastname: Singru
authors.forename: Ranjith
authors.initials: R
authors.lastname: Padinhateeri
authors.forename: Samir K
authors.initials: SK
authors.lastname: Maji
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D019295:Computational Biology; D006801:Humans; D008297:Male; D056004:Molecular Dynamics Simulation; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010902:Pituitary Gland / Q000166:cytology; D055503:Protein Multimerization; D055550:Protein Stability; D020836:Protein Structure, Quaternary; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D022142:Secretory Vesicles / Q000378:metabolism*; D001615:beta-Endorphin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone