Τίτλος:
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
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © Springer Nature Switzerland AG 2020.
Συγγραφείς:
Raftopoulou, S.
Nicolaides, N.C.
Papageorgiou, L.
Amfilochiou, A.
Zakinthinos, S.G.
George, P.
Eliopoulos, E.
Chrousos, G.P.
Vlachakis, D.
Περιοδικό:
Advances in Experimental Medicine and Biology
Λέξεις-κλειδιά:
cryptochrome 1; cryptochrome 2; glucocorticoid receptor; hydrocortisone; interleukin 6; PER1 protein; PER2 protein; retinoic acid receptor alpha; transcription factor ARNTL; transcription factor CLOCK; tumor necrosis factor; DNA; glucocorticoid receptor; hydrocortisone; intercalating agent; transcription factor ARNTL; transcription factor CLOCK, amino acid sequence; computer model; DNA structure; homeostasis; hypothalamus hypophysis adrenal system; insomnia; molecular docking; molecular dynamics; priority journal; protein function; protein protein interaction; protein structure; sleep disorder; stress; chemistry; circadian rhythm; computer simulation; genetics; human; hypophysis adrenal system; hypothalamus hypophysis system; inflammation; mental stress; metabolism; pathophysiology; physiology; prevention and control; sleep disorder, ARNTL Transcription Factors; Circadian Rhythm; CLOCK Proteins; Computer Simulation; DNA; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Inflammation; Intercalating Agents; Pituitary-Adrenal System; Receptors, Glucocorticoid; Sleep Wake Disorders; Stress, Psychological
DOI:
10.1007/978-3-030-32633-3_10
