The Tiny Protein That Syncs With The Earth’s Rotation

Oscillations of a 10 nm protein help cells keep in tune with the 24 hour cycles of the Earth.

AsianScientist (Jul. 2, 2015) – A small protein found in cyanobacteria has been found to encode the Earth’s daily 24 hour rotation. These findings, published in Science, could help answer the longstanding question of how the circadian period of biological clocks are determined and might lead to therapies for disorders associated with abnormal circadian rhythms.

In accordance with diurnal changes in the environment (notably light intensity and temperature) resulting from the Earth’s daily rotation around its axis, many organisms regulate their biological activities to ensure optimal fitness and efficiency.

A wide range of studies have investigated the biological clock in organisms ranging from bacteria to mammals. Consequently, the relationship between the biological clock and multiple diseases has been clarified. However, it remains unclear how 24-hour circadian rhythms are implemented.

Previous research showed that in cyanobacteria, the circadian clock can be reconstructed by mixing three clock proteins (KaiA, KaiB, and KaiC) with ATP. A study published in 2007 showed that KaiC ATPase activity—which mediates the ATP hydrolysis reaction—is strongly associated with circadian periodicity, suggesting that the functional structure of KaiC could be responsible for determining the circadian rhythm.

In the present study, a group of researchers led by Professor Shuji Akiyama of the Research Center of Integrative Molecular Systems (CIMoS) found that the temporal profile of KaiC ATPase activity exhibited an attenuating and oscillating component even in the absence of KaiA and KaiB. A close analysis revealed that this signal had a frequency of 0.91 day-1, which approximately coincided with the 24-hour period. Thus, KaiC is the source of a steady cycle that is in tune with the Earth’s daily rotation.

To identify causal structural factors, the N-terminal domain of KaiC was analyzed using high-resolution crystallography. The resultant atomic structures revealed the underlying cause of KaiC’s slowness relative to other ATPases.

“A water molecule is prevented from attacking into the ideal position for the ATP hydrolysis by a steric hindrance near ATP phosphoryl groups. In addition, this hindrance is surely anchored to a spring-like structure derived from polypeptide isomerization,” explained study co-author Dr. Jun Abe.

“ATP hydrolysis, which involves access of a water molecule to the bound ATP and reverse isomerization of the polypeptide, is expected to require a significantly larger amount of free energy than for typical ATP hydrolysis. Thus, the three-dimensional atomic structure discovered in this study explains why the ATPase activity of KaiC is so much lower (by 100- to 1,000,000-fold) than that of typical ATPase molecules.”

The asymmetric atomic-scale regulation proposed by the authors dictates a feedback mechanism that maintains the ATPase activity at a constant low level. This study provides the first atomic-level demonstration that small protein molecules can generate 24-hour rhythms by regulating molecular structure and reactivity.

“The fact that a water molecule, ATP, the polypeptide chain, and other universal biological components are involved in this regulation suggests that humans and other complex organisms may also share a similar molecular machinery,” Akiyama said.

“In the crowded intracellular environment that contains a myriad of molecular signals, KaiC demonstrates long-paced oscillations using a small amount of energy generated through ATP consumption. This clever mechanism for timekeeping in a noisy environment may inspire development of highly efficient and sustainable chemical reaction processes and molecular-system-based information processing.”

The article can be found at: Abe et al. (2015) Atomic-Scale Origins of Slowness in the Cyanobacterial Circadian Clock.


Source: National Institutes of Natural Sciences.
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