An international team of researchers used an X-ray laser at the Department of Energy’s SLAC National Accelerator Laboratory to create the first detailed maps of two melatonin receptors that tell our bodies when to go to sleep or wake up and guide other biological processes.
An international team of researchers used an X-ray laser at the Department of Energy’s SLAC National Accelerator Laboratory to create the first detailed maps of two melatonin receptors that tell our bodies when to go to sleep or wake up and guide other biological processes. A better understanding of how they work could enable researchers to design better drugs to combat sleep disorders, cancer and Type 2 diabetes. Their findings were published in two papers today in Nature.
The team, led by the University of Southern California, used X-rays from SLAC’s Linac Coherent Light Source (LCLS) to map the receptors, MT1 and MT2, bound to four different compounds that activate them: an insomnia drug, a drug that mixes melatonin with the antidepressant serotonin, and two melatonin analogs.
They discovered that both melatonin receptors contain narrow channels embedded in the fatty membranes of the cells in our bodies. These channels only allow melatonin – which can exist in both water and fat – to pass through and bind to the receptors, blocking serotonin, which has a similar structure but is only happy in watery environments. They also uncovered how some much larger compounds may only target MT1 and not MT2, despite the structural similarities between the two receptors. This should inform the design of drugs that selectively target MT1, which so far has been challenging.
Read more at Stanford University
Image: The behavior of humans and all animals is governed by a variety of natural cycles. The shift of seasons, tides, and day and night influences animal breeding and mating, predator-prey relationships, migration and foraging. Melatonin, depicted as a constellation in the night sky, is the key molecule that allows one of the most stable of these external cycles, a 24-hour day-night rhythm, to be correlated to an internal cycle, with responses at the level of individual cells and the whole animal. High melatonin levels during night time induce sleep-promoting properties by acting through melatonin receptors, depicted in the central reference point of the image composition. (Yekaterina Kadyshevskaya/Bridge Institute of the University of Southern California)
