Department of Biosciences and Bioengineering, Wadhwani Research Centre for Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India.
PLoS One. 2012;7(3):e31924. doi: 10.1371/journal.pone.0031924. Epub 2012 Mar 5.
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.
肽/蛋白激素可以作为无毒性的淀粉样结构储存在垂体分泌颗粒中。ACTH 和 β-内啡肽是两种重要的储存在垂体分泌颗粒中的肽类激素。在这里，我们研究了 ACTH 和 β-内啡肽之间的分子相互作用及其以淀粉样聚集物的形式共定位。虽然已知 ACTH 是 ACTH-β-内啡肽聚集物的一部分，但 ACTH 本身在各种合理条件下都不能聚合形成淀粉样纤维。我们使用全原子分子动力学模拟研究了 ACTH-β-内啡肽系统、β-内啡肽-only 系统和 ACTH-only 系统中的早期分子相互作用事件。我们发现 β-内啡肽和 ACTH 形成了一个相互作用单元，而在 ACTH-only 系统中，ACTH 分子之间几乎没有相互作用。我们的数据表明，ACTH 不仅参与与 β-内啡肽的相互作用，而且还增强了整个系统混合寡聚物的稳定性。
