A major step toward understanding the cellular clock was taken by UT Southwestern Medical Center researchers by mapping for the first time the atomic-level architecture of a key component of the timekeeper that governs the body's daily rhythms.
The daily, or circadian, cycles guided by the body's clocks affect our ability to get a good night's sleep, how fast we recover from jet lag, and even the best time to give cancer treatments, said, senior author of the Science
study published online and a pioneer in the study of circadian rhythms.
Understanding the structure of the cellular clock could lead to better treatments for insomnia, diabetes, and even cancer.
"The clock is found in virtually every cell of the body, and is important for controlling many different metabolic functions," said Dr. Takahashi, chairman of neuroscience and a Howard Hughes Medical Institute (HHMI) investigator at UT Southwestern.
Mapping the 3-D structure of the key component in the cellular clock - called the CLOCK:BMAL1 transcriptional activator complex - will have a great impact on the study of circadian rhythms and in other areas like toxicology and the growth of nerve cells, in which proteins in the same family play central roles, he said.
"Ultimately, we have to go to the atomic level to really understand how these proteins work" Dr. Takahashi said.
The Takahashi laboratory has spent years determining the 3-D structure of the CLOCK:BMAL1 complex using X-ray crystallography. The breakthrough came in the spring of 2011 when Yogarany Chelliah, an HHMI research specialist at UT Southwestern, was able to crystallize the proteins.
The researchers found that the CLOCK protein is tightly wrapped around the BMAL1 protein in an unusually asymmetrical fashion. They identified three distinct areas for interactions between CLOCK and BMAL1 as well as regions for interactions with other molecules that might affect the cellular clock by changing the sleep-wake cycle or other body processes that depend on circadian rhythm, he said.