“Same” formula, different outcome - key features of a successful JH-receptor ligand

Image description: The double bond geometry of juvenile hormone is critical for receptor activation in Drosophila (credit: Martina Hajduskova, www.biographix.cz)

Juvenile hormone (JH) is one of the key regulators of insect development. It is produced during larval growth in order to prevent precocious metamorphosis. Intracellular mediators of JH signaling are JH receptors, recently discovered as basic helix-loop-helix (bHLH)/PAS transcription factors. Upon JH binding, the receptor forms a heterodimer with its binding partner (Taiman) and the resulting complex activates target genes. Several homologs of native JH have been found in different insect and related arthropod species. This study takes a systematic look at the affinity of a Drosophila JH-receptor, known as germ cell-expressed (Gce), for a set of native and synthetic JH analogs. We characterize the potency of each ligand in terms of Gce binding, its activity in a cell-based reporter assay and its morphogenetic effects on fly development. Both in vitro and in vivo results mutually confirm a remarkable stereoselectivity of Gce receptor and its strong preference for the native ligand conformation. Proper double-bond geometry of the natural ligand is critical for a tight receptor binding. Interestingly, the Gce receptor can also be activated by chemically unrelated synthetic agonists commonly used as JH-mimicking insecticides. The molecular basis of these interactions is subject of further research.

Bittová L., Jedlička P., Dracinsky M., Kirubakaran P., Vondrášek J., Hanus R., Jindra M. (2018) Exquisite ligand stereoselectivity of a Drosophila juvenile hormone receptor contrasts with its broad agonist repertoire. Journal of Biological Chemistry in press.
DOI: 10.1074/jbc.RA118.005992