Project description
Transcription factors of the basic helix-loop-helix Per-Arnt-Sim (bHLH-PAS) family are critically important for animal development and physiology. Certain bHLH-PAS proteins are intracellular sensors or receptors of small molecules including environmental xenobiotics, pesticides, or endogenous metabolites and hormones. Insects possess a unique signaling system with a sesquiterpenoid juvenile hormone (JH) that activates a bHLH-PAS receptor (JHR) through interaction with its ligand binding pocket. We propose a novel activation mechanism which involves ligand-controlled release of folded and active JHR from heat shock protein 90 (Hsp90) chaperone. In the current proposal, we plan to test the mechanism by interdisciplinary approach, building on applicants’ complementary expertise in structural biology and biophysics (RT) and in molecular biology of JH signaling (MJ). This information will not only address the knowledge gap in the vital hormonal signaling of insects but will bear relevance for understanding function of ligand-activated bHLH-PAS transcription factors in general and their modulation by synthetic ligands.
This is a collaboration with Prof. Jindra from the Institute of Entomology
For further information see also https://www.pnas.org/doi/full/10.1073/pnas.2215541119
https://www.sciencedirect.com/science/article/pii/S2214574524000762