0000000000149799
AUTHOR
Eva Wolf
How is the inner circadian clock controlled by interactive clock proteins?
AbstractMost internationally travelled researchers will have encountered jetlag. If not, working odd hours makes most of us feel somehow dysfunctional. How can all this be linked to circadian rhythms and circadian clocks? In this review, we define circadian clocks, their composition and underlying molecular mechanisms. We describe and discuss recent crystal structures of Drosophila and mammalian core clock components and the enormous impact they had on the understanding of circadian clock mechanisms. Finally, we highlight the importance of circadian clocks for the daily regulation of human/mammalian physiology and show connections to overall fitness, health and disease.
Influence of mental stress and environmental toxins on circadian clocks : implications for redox regulation of the heart and cardioprotection
Risk factors in the environment such as air pollution and mental stress contribute to the development of chronic non-communicable disease. Air pollution was identified as the leading health risk factor in the physical environment, followed by water pollution, soil pollution/heavy metals/chemicals and occupational exposures, however neglecting the non-chemical environmental health risk factors (e.g. mental stress and noise). Epidemiological data suggest that environmental risk factors are associated with higher risk for cardiovascular, metabolic and mental diseases, including hypertension, heart failure, myocardial infarction, diabetes, arrhythmia, stroke, depression and anxiety disorders. W…
Two light sensors decode moonlight versus sunlight to adjust a plastic circadian/circalunidian clock to moon phase
AbstractMany species synchronize their physiology and behavior to specific hours. It is commonly assumed that sunlight acts as the main entrainment signal for ~24h clocks. However, the moon provides similarly regular time information, and increasingly studies report correlations between diel behavior and lunidian cycles. Yet, mechanistic insight into the possible influences of the moon on ~24hr timers is scarce.We studiedPlatynereis dumeriliiand uncover that the moon, besides its role in monthly timing, also schedules the exact hour of nocturnal swarming onset to the nights’ darkest times. Moonlight adjusts a plastic clock, exhibiting <24h (moonlit) or >24h (no moon) periodicity. Abun…
Structural and mechanistic insights into the interaction of the circadian transcription factor BMAL1 with the KIX domain of the CREB-binding protein
JBC papers in press xx, 16604-16619 (2019). doi:10.1074/jbc.RA119.009845
IM30 IDPs form a membrane protective carpet upon super-complex disassembly
AbstractMembers of thephage shock protein A(PspA) family, including theinner membrane-associated protein of 30 kDa(IM30), are suggested to stabilize stressed cellular membranes. Furthermore, IM30 is essential in thylakoid membrane-containing chloroplasts and cyanobacteria, where it is involved in membrane biogenesis and/or remodeling. While it is well known that PspA and IM30 bind to membranes, the mechanism of membrane stabilization is still enigmatic. Here we report that ring-shaped IM30 super-complexes disassemble on membranes, resulting in formation of a membrane-protecting protein carpet. Upon ring dissociation, the C-terminal domain of IM30 unfolds, and the protomers self-assemble on …
Interaction of Circadian Clock Proteins CRY1 and PER2 Is Modulated by Zinc Binding and Disulfide Bond Formation
SummaryPeriod (PER) proteins are essential components of the mammalian circadian clock. They form complexes with cryptochromes (CRY), which negatively regulate CLOCK/BMAL1-dependent transactivation of clock and clock-controlled genes. To define the roles of mammalian CRY/PER complexes in the circadian clock, we have determined the crystal structure of a complex comprising the photolyase homology region of mouse CRY1 (mCRY1) and a C-terminal mouse PER2 (mPER2) fragment. mPER2 winds around the helical mCRY1 domain covering the binding sites of FBXL3 and CLOCK/BMAL1, but not the FAD binding pocket. Our structure revealed an unexpected zinc ion in one interface, which stabilizes mCRY1-mPER2 int…