DNA：Clock/Bmal1 复合物的结构研究为皮质醇、hGR 和 HPA 轴在应激管理和睡眠障碍中的作用提供了线索。
Structural Study of the DNA: Clock/Bmal1 Complex Provides Insights for the Role of Cortisol, hGR, and HPA Axis in Stress Management and Sleep Disorders.
机构信息
Genetics and Computational Biology Group, Laboratory of Genetics, Department of Biotechnology, Agricultural University of Athens, Athens, Greece.
Affidea Healthcare Company, Athens, Greece.
出版信息
Adv Exp Med Biol. 2020;1195:59-71. doi: 10.1007/978-3-030-32633-3_10.
Herein, we deploy an in silico pipeline of structural bioinformatics, thermodynamics, and molecular dynamics to investigate the role of cortisol in circadian rhythms, biorhythms, stress response, and even sleep disorders. Our study shows that high concentrations of cortisol intercalate in the minor groove of DNA. This phenomenon widens the adjacent major grooves and provides the Clock/Bmal1 complex with more space to dock and interact with DNA. Then, the strong charges of cortisol pull the alpha helices of the Clock/Bmal1 complex and bend it inward, thus establishing stronger interactions and prolonged signaling. Our results indicate that elevated cortisol levels play an important role in stress, inflammation, and sleep disorders as a result of prolonged and stronger dsDNA - Clock/Bmal1 interactions.
在此，我们采用结构生物信息学、热力学和分子动力学的计算流程来研究皮质醇在昼夜节律、生物节律、应激反应甚至睡眠障碍中的作用。我们的研究表明，高浓度的皮质醇会嵌入 DNA 的小沟中。这种现象会拓宽相邻的大沟，为 Clock/Bmal1 复合物提供更多的空间来与 DNA 对接和相互作用。然后，皮质醇的强电荷拉动 Clock/Bmal1 复合物的α螺旋向内弯曲，从而建立更强的相互作用和延长的信号转导。我们的结果表明，由于 dsDNA-Clock/Bmal1 相互作用的延长和增强，升高的皮质醇水平在应激、炎症和睡眠障碍中起着重要作用。
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