Rhodopsin is the mammalian dim light photoreceptor and is also the canonical model for G protein-coupled receptors. Activation of rhodopsin occurs when the covalently bound inverse agonist, retinal, absorbs a photon and undergoes an 11-cis to all-trans isomerization. A critical component of the visual cycle occurs with hydrolytic release of all-trans retinaldehyde and subsequent uptake of 11-cis retinaldehyde to re-form the Schiff base linkage with Lys296 in the apoprotein opsin. Two pores exist on the outer surface of the retinal binding pocket, as seen from the crystal structures of opsin [1], and could serve as potential transport pathways. Our hypothesis is that intermolecular forces between opsin and retinaldehyde drive interactions between ligand, membrane protein, and the lipid bilayer and facilitate retinal uptake and release. We tested this hypothesis using AutoDock Vina and AutoDock4 to identify key ligand-receptor interactions through both pores and within the opsin binding pocket. Our results suggest that retinal undergoes unidirectional uptake through Pore A and release through Pore B, in agreement with a previous study [2]. The most favorable binding affinities for each pore were found when 11-cis retinal straddled Pore A and all-transretinal straddled Pore B. Retinal uptake occurs with entry of the �-ionone ring into Pore A, and subsequent release takes place when the �-ionone ring exits through Pore B. In addition, mutation of Lys296 to the less sterically hindered Gly296 produced more negative binding affinities with identical retinal orientations, making a long-axis flip unlikely and supporting a unidirectional model. These findings are significant in developing our understanding of the photocycle and how retinal interacts with rhodopsin.[1] Park, J.H., et al. (2008) Nature ?454:183.[2] Piechnick, R., et al. (2012) PNAS 109:5249.

Uptake and release pathways of retinal in the rhodopsin photocycle

246th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.