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.

Figure 1

Stereoview showing the secondary and tertiary structure of rhodopsin. The helices are labeled I–VIII. The retinal chromophore is shown in red. The molecule is drawn in the orientation usual for GPCRs with the extracellular surface at the top. Figure drawn using MOLMOL (60).

Figure 2

Stereoview showing regions of the at1 angiotensin receptor involved in ligand binding (red), signal propagation (green), and G protein binding (blue). The residues with atoms shown as spheres are from the crystallographic model of rhodopsin, but their positions were chosen on the basis of a tabulation of important residues in the at1 angiotensin receptor (77). Figure drawn using MOLMOL (60).

Figure 3

Stereoview of the ERY motif in rhodopsin. E3.49[134], R3.50[135], and Y3.51[136] are shown in ball-and-stick mode enclosed in a van der Waals envelope. E6.30[247] is also shown with its hydrogen bond to R3.50[135]. Figure drawn using MOLMOL (60).