title: Altered functionality in rhodopsin point mutants associated with retinitis pigmentosa.
abstract: Point mutations found in rhodopsin associated with the retinal degenerative disease retinitis pigmentosa have been expressed in mammalian COS-1 cells, purified, and characterised. The mutations characterised-most of them for the first time-have been Met44Thr, Gly114Asp, Arg135Leu, Val137Met, and Pro171Leu in the transmembrane domain; Leu328Pro and Ala346Pro in the C-terminal tail of the cytoplasmic domain; and Gly106Trp in the intradiscal domain. Several of these mutations cause misfolding which results in impaired 11-cis-retinal binding. Two of them, Met44Thr and Val137Met, show spectral and structural features similar to those of wild type rhodopsin (Type I mutants) but significantly increased transducin initial activation rates. We propose that, in the case of these mutants, abnormal functioning resulting in faster activation kinetics could also play a role in retinitis pigmentosa by altering the stoichiometric balance of the different proteins involved in the phototransduction biochemical reactions.
authors.affiliation: Unitat de Biofísica, Departament de Bioquímica i de Biologia Molecular, Universitat Autònoma de Barcelona, 08193 Bellaterra, Catalonia, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Andrés
authors.forename: Pere
authors.initials: P
authors.lastname: Garriga
authors.forename: Joan
authors.initials: J
authors.lastname: Manyosa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D003593:Cytoplasm / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D006898:Hydroxylamines / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D017354:Point Mutation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012174:Retinitis Pigmentosa / Q000235:genetics*; D012243:Rhodopsin / Q000235:genetics* / Q000378:metabolism; D017299:Rod Opsins / Q000235:genetics; D013053:Spectrophotometry; D015293:Transducin / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D006898:Hydroxylamines; D017299:Rod Opsins; D012243:Rhodopsin; D015293:Transducin