title: Rhodopsin mutations responsible for autosomal dominant retinitis pigmentosa. Clustering of functional classes along the polypeptide chain.
abstract: Over 40 mutations in the rhodopsin gene have been identified in patients with autosomal dominant retinitis pigmentosa. Twenty-one of these mutations have been introduced into a human rhodopsin cDNA by site-directed mutagenesis, and the encoded proteins have been produced by transfection of a human embryonic kidney cell line (293S). Three of the mutant proteins (G51V, V345M, and P347S) resemble the wild type in yield, regenerability with 11-cis-retinal, and accumulation in the plasma membrane (class I). The remaining 18 mutant proteins are produced at lower levels, regenerate variably or not at all with 11-cis-retinal, and accumulate partially or predominantly in the endoplasmic reticulum (class II). Together with an earlier analysis of 13 mutant rhodopsins (Sung, C.-H., Schneider, B., Agarwal, N., Papermaster, D.S., and Nathans, J. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 8840-8844), these experiments define distinct classes of biochemical defects in human rhodopsin and further show that amino acid substitutions in class II reside within the transmembrane and extracellular domains, whereas class I mutants cluster in the first transmembrane domain and at the extreme carboxyl terminus.
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: C H
authors.initials: CH
authors.lastname: Sung
authors.forename: C M
authors.initials: CM
authors.lastname: Davenport
authors.forename: J
authors.initials: J
authors.lastname: Nathans
mesh_terms: D018076:DNA, Complementary; D005799:Genes, Dominant; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics; D009154:Mutation; D010455:Peptides / Q000737:chemistry; D012174:Retinitis Pigmentosa / Q000235:genetics*; D012243:Rhodopsin / Q000737:chemistry / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D008565:Membrane Proteins; D010455:Peptides; D012243:Rhodopsin