By Martin Primeau

There are thousands of proteins hidden in every cell and that bind to each other to transmit information. This communication often involves 2 proteins at a time, but sometimes there are 3 or more! Some of these assemblies play key roles in signaling and the control of cell proliferation, and therefore it is important to be able to detect their formation or their dissociation.

That is precisely the goal of the new method of detection christened BRETFect, which was developed by an interdisciplinary team bringing together several IRIC principal investigators, namely professors Michel Bouvier, Étienne Gagnon and Sylvie Mader, as well as Dr. David Cotnoir-White, who carried out the work during his PhD thesis in Professor Mader’s lab. The group recently unveiled the proof of principle of the approach, and demonstrated its ability to generate new knowledge in the prestigious scientific journal Proceedings of the National Academy of Sciences.

This approach combines existing techniques in an innovative way to measure how proteins interact with each other. It rests on the use of 3 luminescent proteins, each one coupled with the 3 proteins studied. In the event that those 3 proteins combine with each other to form a complex, the trio of luminescent proteins work together to emit a light that the investigators detect in real time, right inside the cells, until the complex is disassembled.

The authors notably assessed how a hormone, estradiol, stimulates the assembly of an active complex formed by the estrogen receptor, which is a therapeutic target in two thirds of breast cancers. There are two versions of that receptor, which have different properties but can associate with each other and with proteins that are essential for their distinct biological effects in breast cancer. Thanks to BRETFect, the investigators revealed the impact of natural ligands and drugs used for treating breast cancer on the various possible complexes.

This approach should greatly facilitate the development of new drugs that can more accurately target active protein complexes.

Read the full article here.