A concept for G protein activation by G protein-coupled receptor dimers: the transducin/rhodopsin interface

Abstract

G protein-coupled receptors (GPCRs) are ubiquitous and essential in modulating virtually all physiological processes. These receptors share a similar structural design consisting of the seven-transmembrane alpha-helical segments. The active conformations of the receptors are stabilized by an agonist and couple to structurally highly conserved heterotrimeric G proteins. One of the most important unanswered questions is how GPCRs couple to their cognate G proteins. Phototransduction represents an excellent model system for understanding G protein signaling, owing to the high expression of rhodopsin in rod photoreceptors and the multidisciplinary experimental approaches used to study this GPCR. Here, we describe how a G protein (transducin) docks on to an oligomeric GPCR (rhodopsin), revealing structural details of this critical interface in the signal transduction process. This conceptual model takes into account recent structural information on the receptor and G protein, as well as oligomeric states of GPCRs.

Crystal structure of the ligand-free G-protein-coupled receptor opsin

“…Similar dimeric arrangements were found in previous structure determinations from two dimensional and three dimensional rhodopsin crystals [68,114] and rhodopsin models [115]. Based on atomic force microscopic studies [116], a model with TM4 and TM5 as interface of a physiological rhodopsin dimer was proposed [116,117,118].…”

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

“…Several groups have started to attempt this model, based on the X-ray structures of G-proteins 16,17,[83][84][85][86][87][88] and we believe that the simulation results here may lead to speculation about the nature of the interfacial coupling between these domains. [89][90][91][92][93][94][95] In particular, we suggest that the shift in the surface properties of the rhodopsin protein on activation will be found to create a much less favorable environment for protein-protein interaction.…”

Efficient Coupling of Transducin to Monomeric Rhodopsin in a Phospholipid Bilayer

“…The coordinates for rhodopsin (61) and transducin (62) were obtained from the RCSB Protein Data Bank, accession number 1F88 and 1GOT, respectively. The conceptual model of a dimeric rhodopsin, where one molecule is activated, with a single G t was previously proposed by Filipek et al (52).…”