title: Amino acid conservation and interactions in rhodopsin: probing receptor activation by NMR spectroscopy.
abstract: Rhodopsin is a classical two-state G protein-coupled receptor (GPCR). In the dark, its 11-cis retinal chromophore serves as an inverse agonist to lock the receptor in an inactive state. Retinal-protein and protein-protein interactions have evolved to reduce the basal activity of the receptor in order to achieve low dark noise in the visual system. In contrast, absorption of light triggers rapid isomerization of the retinal, which drives the conversion of the receptor to a fully active conformation. Several specific protein-protein interactions have evolved that maintain the lifetime of the active state in order to increase the sensitivity of this receptor for dim-light vision in vertebrates. In this article, we review the molecular interactions that stabilize rhodopsin in the dark-state and describe the use of solid-state NMR spectroscopy for probing the structural changes that occur upon light-activation. Amino acid conservation provides a guide for those interactions that are common in the class A GPCRs as well as those that are unique to the visual system. This article is part of a Special Issue entitled: Retinal Proteins - You can teach an old dog new tricks.
authors.affiliation: Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5215, USA.
authors.forename: Andreyah
authors.initials: A
authors.lastname: Pope
authors.affiliation: Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5215, USA.
authors.forename: Markus
authors.initials: M
authors.lastname: Eilers
authors.affiliation: School of Biological Sciences, University of Essex, Wivenhoe Park, Essex CO4 3SQ, UK.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Reeves
authors.affiliation: Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5215, USA. Electronic address: steven.o.smith@stonybrook.edu.
authors.forename: Steven O
authors.initials: SO
authors.lastname: Smith
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D006860:Hydrogen Bonding; D007536:Isomerism; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012172:Retinaldehyde / Q000737:chemistry* / Q000378:metabolism; D012243:Rhodopsin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D012243:Rhodopsin; D012172:Retinaldehyde
keywords: GPCR; Solid-state NMR spectroscopy; Visual pigment