Schematic plot of a system with a movable wall.

Chromophore hydrolysis and release from photoactivated rhodopsin in native membranes

John D. Hong, David Salom, Michal A. Kochman, Krzysztof Palczewski

PNAS, 2022


Vision starts when a photon isomerizes the 11-cis-retinylidene chromophore of rhodopsin to initiate phototransduction. The all-trans-retinylidene product is hydrolyzed and all-trans-retinal released, allowing rebinding of 11-cis-retinal to regenerate rhodopsin for sustained vision. Subsequently, all-trans-retinal is cleared, preventing aldehyde toxicity by reduction to all-trans-retinol. Defects in these metabolic processes could lead to severe retinopathies. Studying the biochemistry of key proteins responsible for these fundamental steps of vision in their native membrane environments has remained challenging. Using rapid quantitative chemical and analytical methods, we directly captured and quantified the kinetics and energetics of these essential biochemical processes occurring in native membranes. Our results shed light on the entire rhodopsin photocycle and chromophore regeneration and are broadly applicable to other retinylidene proteins.

Full article