title: Biochemical and physiological properties of rhodopsin regenerated with 11-cis-6-ring- and 7-ring-retinals.
abstract: Phototransduction is initiated by the photoisomerization of rhodopsin (Rho) chromophore 11-cis-retinylidene to all-trans-retinylidene. Here, using Rho regenerated with retinal analogs with different ring sizes, which prevent isomerization around the C(11)=C(12) double bond, the activation mechanism of this G-protein-coupled receptor was investigated. We demonstrate that 11-cis-7-ring-Rho does not activate G-protein in vivo and in vitro, and that it does not isomerize along other double bonds, suggesting that it fits tightly into the binding site of opsin. In contrast, bleaching 11-cis-6-ring-Rho modestly activates phototransduction in vivo and at low pH in vitro. These results reveal that partial activation is caused by isomerization along other double bonds in more rigid 6-locked retinal isomers and protonation of key residues by lowering pH in 11-cis-6-ring-Rhos. Full activation is not achieved, because isomerization does not induce a complete set of conformational rearrangements of Rho. These results with 6- and 7-ring-constrained retinoids provide new insights into Rho activation and suggest a potential use of locked retinals, particularly 11-cis-7-ring-retinal, to inactivate opsin in some retinal degeneration diseases.
authors.affiliation: Department of Ophthalmology, University of Washington, Seattle, Washington 98195.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kuksa
authors.affiliation: Institut für Medizinische Physik und Biophysik, Universitätsklinikum Charité, Humboldt Universität zu Berlin, D-10098 Berlin, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Bartl
authors.affiliation: Department of Ophthalmology, University of Washington, Seattle, Washington 98195.
authors.forename: Tadao
authors.initials: T
authors.lastname: Maeda
authors.affiliation: Department of Ophthalmology, University of Washington, Seattle, Washington 98195.
authors.forename: Geeng-Fu
authors.initials: GF
authors.lastname: Jang
authors.affiliation: Institut für Medizinische Physik und Biophysik, Universitätsklinikum Charité, Humboldt Universität zu Berlin, D-10098 Berlin, Germany.
authors.forename: Eglof
authors.initials: E
authors.lastname: Ritter
authors.affiliation: Institut für Medizinische Physik und Biophysik, Universitätsklinikum Charité, Humboldt Universität zu Berlin, D-10098 Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Heck
authors.affiliation: Department of Ophthalmology, University of Washington, Seattle, Washington 98195.
authors.forename: J
authors.initials: J
authors.lastname: Preston Van Hooser
authors.affiliation: Department of Ophthalmology, University of Washington, Seattle, Washington 98195.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
authors.affiliation: International Institute of Molecular and Cell Biology and Department of Chemistry, University of Warsaw, Warsaw PI-02109, Poland.
authors.forename: Sławomir
authors.initials: S
authors.lastname: Filipek
authors.affiliation: Department of Chemistry, University of Washington, Seattle, Washington 98195, and.|Department of Biochemistry, University of Washington, Seattle, Washington 98195.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Gelb
authors.affiliation: Institut für Medizinische Physik und Biophysik, Universitätsklinikum Charité, Humboldt Universität zu Berlin, D-10098 Berlin, Germany.
authors.forename: Klaus Peter
authors.initials: KP
authors.lastname: Hofmann
authors.affiliation: Department of Ophthalmology, University of Washington, Seattle, Washington 98195.|Department of Pharmacology, University of Washington, Seattle, Washington 98195.|Department of Chemistry, University of Washington, Seattle, Washington 98195, and.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Palczewski
mesh_terms: D000818:Animals; D006863:Hydrogen-Ion Concentration; D051379:Mice; D010766:Phosphorylation; D011487:Protein Conformation; D012162:Retinal Degeneration; D012172:Retinaldehyde / Q000378:metabolism*; D012243:Rhodopsin / Q000096:biosynthesis* / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D012243:Rhodopsin; D012172:Retinaldehyde