Biophysical Society Thematic Meeting | Bucharest 2026

Biophysics of Membrane Reactions in Brian

Tuesday Speaker Abstracts

CONFORMATIONAL ENSEMBLES OF RHODOPSIN-G PROTEIN COMPLEXES REVEAL LIGHT PERCEPTION AND GPCR SIGNALING MECHANISMS Ching-Ju Tsai Paul Scherrer Institute, Laboratory of Biomolecular Research, Villigen, Switzerland Animal vision relies on opsins, a specialized class of G protein-coupled receptors (GPCRs) that detect light through covalent binding to the chromophore retinal. In the inactive state, opsins typically bind 11-cis retinal as an inverse agonist; upon photon absorption, retinal isomerizes to all-trans retinal, triggering receptor activation and downstream G protein-mediated signaling cascades. This talk integrates structural data from bovine rhodopsin (Rho) and jumping spider rhodopsin (JSR) to elucidate the conformational nuances underlying their activation mechanisms and signaling pathways. Rho, essential for vertebrate night vision, couples to the Gi/o/t subtype of G proteins and operates as a monostable (bleachable) opsin: following activation, all-trans retinal dissociates, requiring rebinding of 11-cis retinal for renewed function. In contrast, JSR is Gq-coupled and bistable, enabling reversible switching between inactive and active states via distinct wavelengths of light—absorbing a second photon to revert the chromophore without dissociation. Sequence alignments reveal JSR highest similarity to melanopsin among all human opsins, positioning it as a structural proxy for this non-visual photoreceptor involved in circadian entrainment. Drawing from our cryo-EM and crystallographic studies, I will highlight three key aspects: (1) differences in the retinal binding pocket that dictate mono- versus bistability, including stabilizing interactions that prevent chromophore release in bistable systems; (2) G protein binding interfaces, revealing subtype-specific selectivity; and (3) multiple active-state conformations of the Rho-Gi complex, captured using stabilizing Fab fragments (Fab79, Fab16, and Fab13). Together, these insights deepen our understanding of light perception in animals and GPCR/G protein-mediated signal transduction.

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