04.05.17 12:19

Structure of ancient biological clock unveiled

A team of German and Dutch researchers has unveiled the mechanism of one of the oldest biological clocks in Earth’s history in cyanobacteria. With the help of state-of-the-art molecular structural analysis techniques, the researchers at the Max Planck Institute of Biochemistry in Martinsried and the University of Utrecht, together with Junior Professor Ilka Maria Axmann from Heinrich Heine University Düsseldorf (HHU), succeeded in characterizing three ‘clock’ proteins in detail and understanding their interaction. Their research results have now been published in the journal Science.

Cyanobacteria, also referred to as ‘blue-green algae’, are amongst the oldest organisms on Earth that produce oxygen by means of photosynthesis, thus forming the basis for terrestrial life. Already in 2005, Japanese scientists described that the biological clock of cyanobacteria consists of only three proteins: KaiA, KaiB and KaiC. These proteins make up the basic parts of a precise clockwork and are equivalent to the cogs, springs and balance of a mechanical clock. If energy is introduced into the system – like winding up a clock – these three proteins reproduce the rhythm of day and night without any further external influence. In the test tube, such an isolated system remains stable over weeks. Up until today, however, it was not clear how the three ‘clock’ proteins actually accomplished this together.

In their current study, the researchers from the Max Planck Institute of Biochemistry, the University of Utrecht and HHU set themselves the task of solving this question. To this purpose, they used cutting-edge molecular structural analysis techniques, such as native mass spectrometry and cryo-electron microscopy.

Yet how could the scientists now explain the function of the individual parts? “In order to understand the ticking of the biological clock in cyanobacteria, in the figurative sense we stopped time,” explains Professor Albert Heck from Utrecht, who is leading the research work. To stop the biological clock – to freeze it, so to speak – the researchers kept the clock proteins in the refrigerator for a week.

The researchers then studied the molecular structures of this ‘frozen clock’ with the aid of cryo-electron microscopy and generated a kind of ‘freeze frame’. In this way, they succeeded in identifying the position of these ‘clock’ proteins in the clockwork and understanding how the individual parts – the drive, the spring and the balance – of the biological clock work together.

Native mass spectrometry, then again, made it possible to shed light on the frequency of the complex assembly and degradation of the three proteins KaiA, KaiB and KaiC during a 24-hour cycle and to identify which components of the proteins dictate the rhythm.

The research team led by Junior Professor Ilka Axmann at HHU’s Institute of Synthetic Microbiology produced the cyanobacteria’s unique biochemical clock as a kit comprising the three clock proteins in large quantities. The sequence information of the clock proteins was compared with that stored in a large-scale protein database. From this, certain amino acid residues could be identified that are essential for the clock to function. The importance of these amino acid residues could also be verified by examining how clock proteins work when the sequences have been modified.

Professor Axmann explains the significance of the question: “Why do cyanobacteria need a clock? As phototrophic organisms, they are dependent on the sun’s energy. Timekeeping allows them to predict changes in light conditions and to adjust accordingly their energy production by means of photosynthesis before sunrise or sunset. At night-time, they have to save energy – cyanobacteria do not multiply in the dark – it could be said that they sleep at night.”

Biological clocks are in fact very prevalent. The findings from this study can provide new insights into the evolution of biological rhythms. “They can contribute to deciphering a scientific riddle so far unsolved: Why do we need sleep?” says Professor Axmann.


Original publication

J. Snijder, J.M. Schuller, A. Wiegard, P. Lössl, N. Schmelling, I.M.Axmann, J.M. Plitzko, F. Förster & A.J.R. Heck, Structures of the cyanobacterial circadian oscillator frozen in a fully assembled state, Science, March 2017

Link: science.sciencemag.org/content/355/6330/1181.full


Press release by the Max Planck Institute of Biochemistry:

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