MACKAY & MATTHEWS LAB

Protein structure, function and engineering

Our first step into the world of invertebrate transcription factors…

Dec 29, 2021

As part of a collaboration with Ron Hill (formerly CSIRO – now part of the structural biology discipline here at USyd), Jason and Joel helped out (well, mostly Jason) with Ron’s characterization of the insect juvenile hormone receptor. Along with the ecdysone receptor (which we’re also now working on…), juvenile hormone receptor (JHR) is a ligand-binding transcription factor that binds to its cognate hormone (juvenile hormone!) and is then regulates the expression of thousands of genes involved in Arthropod development and reproduction. That means they’re important for more than a million species and a quarter of the animal biomass in the oceans! JHR has been quite elusive because of difficulties in producing it in a stable form, but Ron and his team were able to purify it – it’s a heterodimer of the proteins Met (methoprene resistant) and Tai (Taiman) and is a member of the bHLH-PAS family of TFs (which are in general notoriously difficult to study) and Jason was able to demonstrate that their purified JHR was indeed a 1:1 heterodimer – using SEC-MALLS. The work was published in J Biol Chem in December:

https://pubmed.ncbi.nlm.nih.gov/34758356/

With Ron now at USyd, we have also begun developing a program focused on the development of safer and more selective insecticides that target hormone-binding TFs – broadening the scope of our years of work on transcription factor biochemistry to address a significant problem.

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