1. MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
2. Department of Ophthalmology, and Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, Florida 32610, USA
3. Present address: The Scripps Research Institute, Department of Cell Biology-MB28, 10666 North Torrey Pines Road, La Jolla, California 92037, USA.

Correspondence to: Gebhard F. X. Schertler¹ Correspondence and requests for materials should be addressed to G.F.X.S. (e-mail: Email: gfx@mrc-lmb.cam.ac.uk).

Abstract

Rhodopsins¹, the photoreceptors in rod cells, are G-protein-coupled receptors with seven hydrophobic segments containing characteristic conserved sequence patterns that define a large family²,³. Members of the family are expected to share a conserved transmembrane structure. Direct evidence for the arrangement of seven -helices was obtained from a 9å projection map of bovine rhodopsin⁴. Structural constraints inferred from a comparison of G-protein-coupled receptor sequences were used to assign the seven hydrophobic stretches in the sequence to features in the projection map⁵. A low-resolution three-dimensional structure of bovine rhodopsin⁶ and two projection structures of frog rhodopsin⁷ confirmed the position of the three least tilted helices, 4, 6 and 7. A more elongated peak of density for helix 5 indicated that it is tilted or bent⁶,⁷, but helices 1, 2 and 3 were not resolved. Here we have used electron micrographs of frozen-hydrated two-dimensional frog rhodopsin crystals to determine the structure of frog rhodopsin. Seven rods of density in the map are used to estimate tilt angles for the seven helices. Density visible on the extracellular side of the membrane suggests a folded domain. Density extends from helix 6 on the intracellular side, and a short connection between helices 1 and 2, and possibly a part of the carboxy terminus, are visible.