title: Retinal Attachment Instability Is Diversified among Mammalian Melanopsins.
abstract: Melanopsins play a key role in non-visual photoreception in mammals. Their close phylogenetic relationship to the photopigments in invertebrate visual cells suggests they have evolved to acquire molecular characteristics that are more suited for their non-visual functions. Here we set out to identify such characteristics by comparing the molecular properties of mammalian melanopsin to those of invertebrate melanopsin and visual pigment. Our data show that the Schiff base linking the chromophore retinal to the protein is more susceptive to spontaneous cleavage in mammalian melanopsins. We also find this stability is highly diversified between mammalian species, being particularly unstable for human melanopsin. Through mutagenesis analyses, we find that this diversified stability is mainly due to parallel amino acid substitutions in extracellular regions. We propose that the different stability of the retinal attachment in melanopsins may contribute to functional tuning of non-visual photoreception in mammals.
authors.affiliation: Department of Life and Coordination-Complex Molecular Science, Institute for Molecular Science, Okazaki, 444-8585, Japan,; Department of Structural Molecular Science, SOKENDAI (The Graduate University for Advanced Studies), Hayama, Kanagawa 240-0193, Japan,. Electronic address: tsukamoh@ims.ac.jp.
authors.forename: Hisao
authors.initials: H
authors.lastname: Tsukamoto
authors.affiliation: Division of Biophysics and Neurobiology, Department of Molecular Physiology, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan,; Department of Physiological Sciences, SOKENDAI (The Graduate University for Advanced Studies), Hayama, Kanagawa 240-0193, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kubo
authors.affiliation: Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, Oregon 97239-3098.
authors.forename: David L
authors.initials: DL
authors.lastname: Farrens
authors.affiliation: Department of Biology and Geosciences, Graduate School of Science, Osaka City University, Osaka 558-8585, Japan.
authors.forename: Mitsumasa
authors.initials: M
authors.lastname: Koyanagi
authors.affiliation: Department of Biology and Geosciences, Graduate School of Science, Osaka City University, Osaka 558-8585, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Terakita
authors.affiliation: Department of Life and Coordination-Complex Molecular Science, Institute for Molecular Science, Okazaki, 444-8585, Japan,; Department of Structural Molecular Science, SOKENDAI (The Graduate University for Advanced Studies), Hayama, Kanagawa 240-0193, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Furutani
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019143:Evolution, Molecular; D005260:Female; D005701:Galago; D014644:Genetic Variation; D006801:Humans; D064175:Lancelets; D008322:Mammals / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism / Q000528:radiation effects; D048530:Papio anubis; D020419:Photoreceptor Cells, Vertebrate / Q000737:chemistry / Q000528:radiation effects; D010802:Phylogeny; D011487:Protein Conformation; D055550:Protein Stability; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000528:radiation effects; D012165:Retinal Ganglion Cells / Q000737:chemistry / Q000528:radiation effects; D012168:Retinal Pigments / Q000737:chemistry / Q000235:genetics / Q000528:radiation effects; D012172:Retinaldehyde / Q000737:chemistry*; D017299:Rod Opsins / Q000737:chemistry* / Q000235:genetics* / Q000528:radiation effects; D012453:Saimiri; D012545:Schiff Bases / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D013112:Spiders; D014981:Xenopus; D000099210:Melanopsin
chemical_list: D011994:Recombinant Proteins; D012168:Retinal Pigments; D012172:Retinaldehyde; D017299:Rod Opsins; D012545:Schiff Bases; D000099210:Melanopsin
keywords: electrophysiology; membrane protein; molecular evolution; non-visual photoreception; photoreceptor; rhodopsin; ultraviolet-visible spectroscopy (UV-visible spectroscopy)