Mapping signal transduction in bistable jumping spider rhodopsin 1

G-protein-coupled receptors are key drug targets due to their role in cellular signaling. Among them, bistable rhodopsins such as the jumping spider rhodopsin 1 (JSR1), are promising for optogenetic applications, but their transduction mechanisms remain poorly understood. In this study, we used microsecond equilibrium molecular dynamics simulations, network analysis, and machine learning to investigate allosteric communication paths between the retinal chromophore and the intracellular G-protein-binding site in JSR1. We analyzed structural differences in three functional states with retinal chromophores in 9-cis, 11-cis, and all-trans configurations. Results revealed that Trp290 is crucial for transmitting the movements of the retinal after isomerization to the G-protein-binding site during JSR1 activation as well as residues along TM6 helix. Overall, these findings advance our understanding of bistable rhodopsins and their potential in light-driven technologies.