Researchers identify structure of circadian clock protein

November 15, 2011 By Krishna Ramanujan
Researchers identify structure of circadian clock protein
The 3-D crystal structure of the dCRY molecule. The C-Terminus is in red. Image: Crane Lab

(PhysOrg.com) -- Feeling jet-lagged? You may need your internal clock reset. New Cornell research has taken a major step toward treating jet lag and other more serious syndromes by advancing our understanding of how circadian rhythms work.

Cornell researchers have identified for the first time the 3-D crystal structure of a protein in (Drosophila) that also facilitates circadian rhythm functions in most higher organisms -- from and plants to animals, including humans.

The study appears in the Nov. 13 issue of the journal Nature.

While the mechanisms of circadian -- or biological -- clocks are complex in humans, many of their key components are shared by such lower species as Drosophila, which serve as a for understanding circadian rhythms.

The protein, called cryptochrome (dCRY), plays a key role in circadian clocks, which get cues from daylight and allow organisms to pace their metabolism on a 24-hour cycle.

Biological clocks regulate such processes as opening and closing of petals and shedding of leaves in plants, for example, and the timing of hunger, waking, excretion and changes in blood pressure in people. Minor disruptions of human clocks can lead to and fatigue, while chronic malfunctions have been associated with some and cancers.

"The aim of the study was to understand the structure of dCRY at the molecular level," which was done by using X-ray crystallography, said co-author Anand Vaidya, a graduate student working in the lab of senior author Brian Crane, professor of chemistry and . Brian Zoltowski, Ph.D. '08, currently an assistant professor at Southern Methodist University, is the paper's lead author.

Identifying the structure of dCRY is "a starting point to understand the function and mechanisms of the protein," Vaidya added.

The main mechanism of the Drosophila involves four types of proteins. Two negative proteins act as inhibitors, suppressing two others, the positive proteins. Without this suppression, the positive proteins activate genes that initiate signaling events and ultimately control the organism's diurnal rhythms. Suppression is prevented by dCRY, which goes into action in the presence of light, binding to the negative proteins and leading to their degradation. This allows the biological clock to reset and the positive proteins to function.

By identifying dCRY's structure, the researchers found that when a small molecule that is bound to dCRY, called a flavin, absorbs light, it helps an arm of the protein, called the C-terminus, to change shape, thus allowing dCRY to bind to the negative proteins. Previous studies have shown that dCRY proteins, and thus , lose their function when the C-terminus is removed.

"Another intriguing aspect of cryptochromes is that they are evolutionarily related to enzymes called photolyases, which use light to repair damage to DNA caused by ultraviolet radiation" from sunlight, said Crane.

The dCRY crystal structure was found to be remarkably similar in structure to photolyases. The C-terminus, for example, lies in exactly the same pocket on the dCRY molecule as that to which damaged DNA attaches when photolyases begin repairs.

Recently, dCRY has also been implicated in magnetosensitivity -- the ability of organisms to sense magnetic fields, including that of the earth. Although more research is needed to better understand this phenomenon, the Cornell study provides a basis to begin to understand the mechanism.

Co-authors include researchers from the Laboratory of Genetics at Rockefeller University in New York. The study was funded by the National Institutes of Health.

Explore further: Finding mechanism behind bacteria's biological clock

Related Stories

Recommended for you

Lab charts the anatomy of three molecular channels

January 23, 2017

Using a state-of-the-art imaging technology in which molecules are deep frozen, scientists in Roderick MacKinnon's lab at Rockefeller University have reconstructed in unprecedented detail the three-dimensional architecture ...

New steps in the meiosis chromosome dance

January 23, 2017

Where would we be without meiosis and recombination? For a start, none of us sexually reproducing organisms would be here, because that's how sperm and eggs are made. And when meiosis doesn't work properly, it can lead to ...

Research describes missing step in how cells move their cargo

January 23, 2017

Every time a hormone is released from a cell, every time a neurotransmitter leaps across a synapse to relay a message from one neuron to another, the cell must undergo exocytosis. This is the process responsible for transporting ...

Immune defense without collateral damage

January 23, 2017

Researchers from the University of Basel in Switzerland have clarified the role of the enzyme MPO. In fighting infections, this enzyme, which gives pus its greenish color, produces a highly aggressive acid that can kill pathogens ...

Provocative prions may protect yeast cells from stress

January 23, 2017

Prions have a notorious reputation. They cause neurodegenerative disease, namely mad cow/Creutzfeld-Jakob disease. And the way these protein particles propagate—getting other proteins to join the pile—can seem insidious.

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

tkjtkj
not rated yet Nov 15, 2011
This is a major advance! How 'clever' of evolution to develop such a system .. and to find that it must have evolved eons ago.
And clever of the authors' team to put it together ..

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.