MSGID: 1:317/3 6279ea8b   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    Chronobiologists identify key circadian clock mechanism in cyanobacteria   
      
      
     Date:   
         May 9, 2022   
     Source:   
         National Institutes of Natural Sciences   
     Summary:   
         The activation and inactivation mechanisms of a key protein   
         involved in the circadian clock system of cyanobacteria -- an   
         important organism in the evolution of such internal clocks --   
         have long eluded scientists. But researchers have now identified   
         how the system is driven.   
      
      
      
   FULL STORY   
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   Researchers have identified a key mechanism involved with the setting   
   of the circadian clock of cyanobacteria -- a model organism for study   
   by chronobiologists due to the organism having one of the earliest   
   circadian systems to evolve, and thus shining a light on how our own   
   such systems work.   
      
      
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   A paper describing the findings appeared in the Proceedings of the   
   National Academy of Sciences on 4th May, 2022.   
      
   Chronobiologists -- researchers who study the timing processes,   
   including circadian clocks, of organisms -- have long been interested   
   in cyanobacteria (aka blue-green algae) as a model organism for   
   investigation, and its KaiC protein in particular.   
      
   The KaiC protein forms a key part of the cyanobacteria's master clock,   
   and regulation of the genes that produce this protein and others it   
   interacts with is crucial for maintaining the bacterium's circadian   
   rhythm, and thus when to engage in its core life processes such as   
   photosynthesis and cell division.   
      
   Further elucidation of how the system works thus shines a light on how   
   circadian clocks work throughout the living world.   
      
   KaiC is an ATPase, an enzyme that initiates (catalyzes) the chemical   
   reaction that splits off a phosphoryl group (an ion containing phosphorus   
   and oxygen) from adenosine triphosphate (ATP) by using a water molecule,   
   a process that releases energy that can then be harnessed to power   
   actions throughout living things.   
      
   But KaiC is a special type of ATPase in that it has a double-domain   
   structure, with one active site (location on an enzyme where the   
   chemical reaction takes place) in one domain and another active site   
   in the other. The cyanobacteria's circadian clock system is governed   
   through a slow and orderly -- but also very complex -- coordination of   
   the two sites.   
      
      
      
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   To do this, the KaiC protein uses two types of ATP molecules to produce   
   diverse chemical reactions and thereby govern the circadian rhythm. The   
   ATP molecules attach themselves to a Walker motif -- a loop structure   
   in proteins that is associated with phosphate binding -- present in the   
   two domains, called N- terminal C1 and C-terminal C2. The ATP molecule   
   bound to the C1 domain is the main source of the ATP hydrolysis reaction   
   whose rate determines the speed of the clock system. In the presence   
   of KaiC's sister proteins KaiA and KaiB, the ATP molecules bound not   
   only in the C1 domain but also in the C2 domain are activated and then   
   inactivated periodically.   
      
   "In recent years, this C1/C2-ATPase interaction of KaiC has become   
   an important research target to achieve a better understanding of   
   the circadian clock system in cyanobacteria," said Shuji Akiyama, a   
   biophysicist with the Institute for Molecular Science at Japan's National   
   Institutes of Natural Sciences, and co- author of the study, "as it   
   closely relates to the clock's properties of oscillation, period-tuning,   
   and adjustment of the system to compensate for the effects of changes   
   in temperature."  A great deal of research has explored KaiC ATPase's   
   biochemistry and structure, but the precise mechanisms of its activation   
   and inactivation until now have remained unknown.   
      
   The researchers used biochemical and structural biology techniques,   
   including substitutions of amino acids in KaiC itself, to characterize   
   the properties and interplay of the dual ATPase active sites. They also   
   performed an analysis of the crystal structure of KaiC to visualize the   
   activated and inactivated forms of the ATP and catalytic water molecules   
   in the C1 domain.   
      
   They found that the N-terminal and C-terminal ATPases communicate with   
   each other through an interface between the N-terminal and C-terminal   
   domains in KaiC. The dual ATPase sites are regulated rhythmically in   
   a concerted or opposing manner depending on the phase of the circadian   
   clock system, to control the assembly and disassembly cycle of the other   
   clock proteins, KaiA and KaiB. The results suggest that the activation   
   of dual KaiC ATPases through an auto-catalytic mechanism (a product of   
   a reaction then becomes a catalyst for the same reaction) contributes   
   to a sudden disassembly at dawn of the protein complexes built over night.   
      
   This is crucial for resetting "subjective night," or what the organism's   
   clock predicts the length of night to be, and then pushing the whole   
   system forward in its cycle.   
      
   Many structural details of the C2-ATPase remain unclear even after the   
   researchers' analysis, partly because they were unable to identify some   
   catalytic water molecules involved, suggesting further areas of research   
   to fine-tune their understanding of the clock system. The researchers   
   were also amazed at the enormous range of activity of the C2-ATPase,   
   which can be suppressed down to zero. The physiological significance of   
   this is also the next important research target for the scientists.   
      
      
   ==========================================================================   
   Story Source: Materials provided by   
   National_Institutes_of_Natural_Sciences. Note: Content may be edited   
   for style and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. Yoshihiko Furuike, Atsushi Mukaiyama, Shin-ichi Koda, Damien Simon,   
         Dongyan Ouyang, Kumiko Ito-Miwa, Shinji Saito, Eiki Yamashita,   
         Taeko Nishiwaki-Ohkawa, Kazuki Terauchi, Takao Kondo,   
         Shuji Akiyama. Regulation mechanisms of the dual ATPase in   
         KaiC. Proceedings of the National Academy of Sciences, 2022; 119   
         (19) DOI: 10.1073/pnas.2119627119   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2022/05/220509112052.htm   
      
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