title: An experimental comparison of human and bovine rhodopsin provides insight into the molecular basis of retinal disease.
abstract: Rhodopsin is the visual pigment that mediates dim-light vision in vertebrates and is a model system for the study of retinal disease. The majority of rhodopsin experiments are performed using bovine rhodopsin; however, recent evidence suggests that significant functional differences exist among mammalian rhodopsins. In this study, we identify differences in both thermal decay and light-activated retinal release rates between bovine and human rhodopsin and perform mutagenesis studies to highlight two clusters of substitutions that contribute to these differences. We also demonstrate that the retinitis pigmentosa-associated mutation G51A behaves differently in human rhodopsin compared to bovine rhodopsin and determine that the thermal decay rate of an ancestrally reconstructed mammalian rhodopsin displays an intermediate phenotype compared to the two extant pigments.
authors.affiliation: Department of Cell and Systems Biology, University of Toronto, Canada.|Department of Ecology and Evolutionary Biology, University of Toronto, Canada.
authors.forename: James M
authors.initials: JM
authors.lastname: Morrow
authors.affiliation: Department of Cell and Systems Biology, University of Toronto, Canada.
authors.forename: Gianni M
authors.initials: GM
authors.lastname: Castiglione
authors.affiliation: Department of Ecology and Evolutionary Biology, University of Toronto, Canada.
authors.forename: Sarah Z
authors.initials: SZ
authors.lastname: Dungan
authors.affiliation: Department of Cell and Systems Biology, University of Toronto, Canada.|Department of Ecology and Evolutionary Biology, University of Toronto, Canada.
authors.forename: Portia L
authors.initials: PL
authors.lastname: Tang
authors.affiliation: Department of Cell and Systems Biology, University of Toronto, Canada.
authors.forename: Nihar
authors.initials: N
authors.lastname: Bhattacharyya
authors.affiliation: Department of Ecology and Evolutionary Biology, University of Toronto, Canada.
authors.forename: Frances E
authors.initials: FE
authors.lastname: Hauser
authors.affiliation: Department of Cell and Systems Biology, University of Toronto, Canada.|Department of Ecology and Evolutionary Biology, University of Toronto, Canada.|Centre for the Analysis of Genome Evolution and Function, University of Toronto, Canada.
authors.forename: Belinda S W
authors.initials: BSW
authors.lastname: Chang
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002417:Cattle; D020022:Genetic Predisposition to Disease; D057809:HEK293 Cells; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D008027:Light; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010802:Phylogeny; D054730:Protein Interaction Domains and Motifs / Q000528:radiation effects; D055550:Protein Stability / Q000528:radiation effects; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012160:Retina / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012243:Rhodopsin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012545:Schiff Bases / Q000737:chemistry; D012995:Solubility / Q000528:radiation effects; D013053:Spectrophotometry
chemical_list: D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D012545:Schiff Bases; D012243:Rhodopsin
keywords: opsin; retinal disease; retinitis pigmentosa; vision; visual pigment