Receptor dynamics open up new possibilities for drug development

Published: 2017-08-09

Novel findings reveal that G protein-coupled receptors, which have previously assumed to be statically configured as monomers or dimers, can switch between the two arrangements under different conditions. This provides new strategies for drug development, as separation or joining may be inhibited or triggered.   

G protein-coupled receptors, a common type of protein in the human body, transmit signals from outside a cell to the inside. For example, they are essential for adrenaline, histamine and dopamine responses. The central functions of G protein-coupled receptors have made them important targets for drugs such as beta-blockers, antihistamines and L-DOPA.

The present study is published in Nature Communications and was conducted by the groups of Gunnar Schulte (KI), Jens Carlsson (Uppsala University/SciLifeLab), and Stefan Wennmalm (KTH/SciLifeLab). It shows for the first time that a G protein-coupled receptor called Frizzled 6 (FZD6) is able to shift between dimeric and monomeric forms. The paper shows that the FZD6 receptors occur as dimers when they are inactive but dissociates into monomers upon stimulation by a signaling molecule, which enables triggering of intracellular signals.

In addition, the research project was carried out in collaboration with the Fluorescence Correlation Spectroscopy facility at SciLifeLab and Hebrew University in Jerusalem, Israel.

Read the press release from Karolinska Institutet