Sidney PhD student’s work published in Nature

Vaithish is the lead author of the work that determined the first high-resolution structure of a G-protein-coupled receptor (GPCR) from the fungal kingdom. This work had been sought after for decades in the scientific world. The structure provides a template for the design of novel drugs against several currently intractable fungal diseases, many of which disproportionately affect people in the developing world.

Vaithish commented, “We have engineered a novel G protein and used cryogenic-electron microscopy to determine the first high resolution structure of a fungal GPCR. The structure not only provides a template for the design of drugs against many intractable fungal diseases that are lethal to humans and damage crop production, but also shows for the first time how a GPCR dimer could be formed through transmembrane interactions and reveals that a GPCR could simultaneously couple to two G proteins. These findings are especially intriguing and inspires my current work on understanding the importance of dimerization and dual G protein-coupling in GPCR signalling and may allow us to target GPCRs better with less side-effects, which is critical considering that about one-third of all FDA-approved drugs target GPCRs.

I felt ecstatic when I finished building the atomic model of this GPCR dimer and could visualise the intricate atomic interactions within the protein, and I am now glad that the whole world could get to experience the same! We hope this structure and the tools developed in this work could set the stage for the new field of fungal GPCR structural biology and may allow us to uncover the secrets of the fungal world”.

Great work, Vaithish!

Vaithish Velazhahan and the first high resolution structure of a fungal GPCR