Structure of rhodopsin and the metarhodopsin I photointermediate.
The structure of the visual pigment rhodopsin in the dark state was first investigated by electron microscopy (EM). More recently, rhodopsin has been crystallised in two different space groups--a tetragonal P4(1) crystal form and a trigonal P3(1) packing arrangement. The structures of the pigment, determined by X-ray crystallography from these two crystal forms, show many similarities, but also significant differences. These differences are most extensive in the G-protein-binding region of the cytoplasmic surface, where the location of the loop between helices 5 and 6 is highly variable. A combination of EM and spin labelling suggests that this loop adopts the native conformation in the P3(1) crystal form. The X-ray structures also show the location of structural water molecules that are important for colour tuning, stabilisation of the ground state and receptor activation, and act as a template for modelling other G-protein-coupled receptors. A major current focus of structural work on rhodopsin is investigation of the activated state of the receptor. After careful spectroscopic characterisation of light activation in two-dimensional crystals, a map of the metarhodopsin I intermediate was obtained by EM from two-dimensional crystals. In addition, NMR studies are providing information about the structure of activated states of rhodopsin. In the future, structural information will show how rhodopsin becomes activated and how it couples to downstream signalling pathways.
Schertler
Gebhard F X
GF
MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK. gfx@mrc-lmb.cam.ac.uk
D000818:Animals; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D011487:Protein Conformation; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012243:Rhodopsin / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D043562:Receptors, G-Protein-Coupled; C013110:metarhodopsins; D012243:Rhodopsin