11 May 2017

Researchers show how cell receptors regulate specific physiological effects

Cell receptors

The physiological processes in our body are regulated by receptors on the cell surface. For the very first time, researchers from the University of Copenhagen have shown how the receptors induce specific cell effects. This opens up for the design of safer drugs with fewer side effects.

The findings can be compared to a complex system of multiple keys and locks, where GPCRs are keys and the G proteins are locks that open different doors – the signalling pathways.
Photo: MRC Laboratory of Molecular Biology in Cambridge

Taste, smell, sight and ability to feel pain. All of these things depend on cell receptors. They are crucial for life as we know it. They enable all living beings to communicate with their surroundings as well as between parts of the body. If cells were not able to communicate, no organism would be larger than one cell. The receptors regulate our physiological functions, and dysfunction causes a number of diseases ranging from cancer to infertility.

For the first time, researchers from the Faculty of Health and Medical Sciences at the University of Copenhagen and MRC Laboratory of Molecular Biology in Cambridge have together revealed how receptors trigger specific physiological responses in the cell. The results have just been published in in the highly esteemed scientific journal Nature.

 “This is a landmark-study. It is the first study of its kind where we reveal how our bodies work on a molecular level. If we want to understand how specific receptor responses are produced, we have to understand how these receptors work. The future perspective is to translate this into the design of safer drugs with fewer side effects. Furthermore, it will inspire many other new studies,” says Professor David Gloriam, Associate Professor at Department of Drug Design and Pharmacology, University of Copenhagen.

‘Barcodes’ control cell signals
The researchers have studied the receptors that constitute the most common drug targets, called G protein coupled-receptors (GPCR’s). 30 percent of the drugs that you can buy at the pharmacy target these receptors. When the GPCR’s are targeted by a drug, they activate a G protein, which then induces a certain physiological effect inside the cell. Therefore, it is necessary to understand what makes the GPCR’s bind to specific G proteins.

“We have identified the patterns of amino acids in the G protein. The patterns make up a kind of ‘selectivity barcodes’ in the G proteins which are then recognized by different GPCR’s. In other words, our findings show the molecular details of how different GPCR’s selectively activate distinct G proteins to trigger specific signaling pathways,” David Gloriam explains.

The more we know about which GPCR’s activate which G proteins and how, the easier it is to design drugs that give only the desired, therapeutic effect and not the unwanted side effects.

The study “Selectivity determinants of GPCR-G-protein binding” has just been published in Nature. It is a collaboration between the Madan M. Babu group, MRC Laboratory of Molecular Biology in Cambridge and the University of Copenhagen.

More information

Press release by MRC Laboratory of Molecular Biology
Associate Professor David Gloriam, email: david.gloriam@sund.ku.dk, telephone: +45 35 33 61 62