Ultrafast structural changes direct the first molecular events of retinal isomerisation and rhodopsin activation.

Abstract

Vision is initiated by the rhodopsin family of light-sensitive G protein-coupled receptors (GPCRs). A photon is absorbed by the 11-cis retinal chromophore of rhodopsin which isomerises within 200 femtoseconds to the all-trans conformation. In this work, we use ultrafast time-resolved crystallography at room temperature to determine how an isomerised twisted all-trans retinal stores the photon energy required to initiate retinal isomerization. The distorted retinal at 1 ps time-delay of photoactivation has reduced its numerous interactions with the amino acids in its binding pocket. The excess of the photon energy is released through an anisotropic protein breathing motion in the direction of the extracellular space. Strikingly, the very early structural motions in the protein side chains of rhodopsin appear in regions involved in later stages of the conserved Class A GPCR activation mechanism. This indicates a conserved energy dissipation pathway and a dual function of the internal hydrogen bond networks of the GPCR linked to its dynamic conformational landscape. Our ultrafast free electron laser measurements shed light on the earliest stages of vision in vertebrates and points to fundamental aspects of the molecular mechanisms of photo activation of retinal proteins.