Three-dimensional structure of an invertebrate rhodopsin and basis for ordered alignment in the photoreceptor membrane

Invertebrate rhodopsins activate a G-protein signalling pathway in microvil lar photoreceptors. In contrast to the transducin-cyclic GMP phosphodiester ase pathway found in vertebrate rods and cones, visual transduction in ceph alopod (squid, octopus, cuttlefish) invertebrates is signalled via Gq and p hospholipase C. Squid rhodopsin contains the conserved residues of the G-pr otein coupled receptor (GPCR) family, but has only 35% identity with mammal ian rhodopsins. Unlike vertebrate rhodopsins, cephalopod rhodopsin is arran ged in an ordered lattice in the photoreceptor membranes. This organization confers sensitivity to the plane of polarized light and also provides the optimal orientation of the linear retinal chromophores in the cylindrical m icrovillar membranes for light capture. Two-dimensional crystals of squid r hodopsin show a rectilinear arrangement that is likely to be related to the alignment of rhodopsins in vivo. Here, we present a three-dimensional structure of squid rhodopsin determine d by cryo-electron microscopy of two-dimensional crystals. Docking the atom ic structure of bovine rhodopsin into the squid density map shows that the helix packing and extracellular plug structure are conserved. In addition, there are two novel structural features revealed by our map. The linear lat tice contact appears to be made by the transverse C-terminal helix lying on the cytoplasmic surface of the membrane. Also at the cytoplasmic surface, additional density may correspond to a helix 5-6 loop insertion found in mo st GPCRs relative to vertebrate rhodopsins. The similarity supports the con servation in structure of rhodopsins (and other G-protein-coupled receptors ) from phylogenetically distant organisms. The map provides the first indic ation of the structural basis for rhodopsin alignment in the microvillar me mbrane. (C) 2001 Academic Press.