The Crystallographic Model of Rhodopsin and Its Use in Studies of Other G Protein–Coupled Receptors

Abstract

G protein-coupled receptors (GPCRs) are integral membrane proteins that respond to environmental signals and initiate signal transduction pathways activating cellular processes. Rhodopsin is a GPCR found in rod cells in retina where it functions as a photopigment. Its molecular structure is known from cryo-electron microscopic and X-ray crystallographic studies, and this has reshaped many structure/function questions important in vision science. In addition, this first GPCR structure has provided a structural template for studies of other GPCRs, including many known drug targets. After presenting an overview of the major structural elements of rhodopsin, recent literature covering the use of the rhodopsin structure in analyzing other GPCRs will be summarized. Use of the rhodopsin structural model to understand the structure and function of other GPCRs provides strong evidence validating the structural model.

Common Structural Basis for Constitutive Activity of the Ghrelin Receptor Family

“…Molecular model of the residues proposed to be part of the structural basis for the high constitutive activity in the ghrelin receptor. A, molecular model of the ghrelin receptor built over the inactive structure of rhodopsin (60,61). The seven helical bundle is displayed without the loops as viewed from the extra-cellular side.…”

How a small change in retinal leads to G‐protein activation: Initial events suggested by molecular dynamics calculations

“…3,[128][129][130] This is especially important due to the large number of important pharmacological targets within the large GPCR family. [131][132][133][134][135][136][137][138][139][140][141][142] In our simulation results, the nature of the coupling between a local conformational change and a large-scale helix and loop change may be similar across the GPCR family. This would imply that the effect of ligand binding to a GPCR is tightly regulated by a coupled set of energetic interactions, in a similar manner to that found within the retinal-rhodopsin system.…”

The supramolecular structure of the GPCR rhodopsin in solution and native disc membranes

“…This structure also allowed construction and validation of numerous prediction models of other GPCRs (reviewed in ref. [38]). Recent biochemical studies demonstrated the existence of detergent-resistant membrane microdomains in ROS and therefore a non-uniform distribution of lipids and proteins [39][40][41].…”