Constitutively active mutants of rhodopsin

@article{Robinson1992ConstitutivelyAM,
  title={Constitutively active mutants of rhodopsin},
  author={Phyllis R. Robinson and George B. Cohen and Eugene A. Zhukovsky and Daniel D. Oprian},
  journal={Neuron},
  year={1992},
  volume={9},
  pages={719-725}
}
Two critical amino acids in the visual pigment rhodopsin are Lys-296, the site of attachment of retinal to the protein through a protonated Schiff base linkage, and Glu-113, the Schiff base counterion. Mutation of Lys-296 or Glu-113 results in constitutive activation of opsin, as assayed by its ability to activate transducin in the absence of added chromophore. We conclude that opsin is constrained to an inactive conformation by a salt bridge between Lys-296 and Glu-113. Recently, one of the… Expand
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  • FEBS letters
  • 2006
TLDR
One important role for preserving the negatively charged glutamate in the third helix of UV pigments is to maintain a less active opsin in a manner similar to rhodopsin. Expand
G PROTEIN-COUPLED
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Several mutations have been described that constitutively activate the apoprotein opsin, and four of them have been shown to cause two different diseases of the retina, retinitis pigmentosa and congenital night blindness. Expand
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TLDR
It is demonstrated that rhodopsin can tolerate a second Lys in the retinal binding pocket and suggest that an evolutionary intermediate with two Lys could allow migration of the Schiff base Lys to a position other than the observed, highly conserved location in the seventh TM helix. Expand
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TLDR
Biochemical analyses suggested that acquiring a new counterion Glu113 could be an essential replacement for not only emergence of efficient activation of G protein but also emergence of red-sensitive visual pigments. Expand
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TLDR
The data suggest that the protonated state of Glu-134 favors binding of rhodopsin to transducin and that Glu/Asp/Arg/Tyr is not titratable in the rhodopin-transducin complex. Expand
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The C9 methyl group of retinal interacts with glycine-121 in rhodopsin.
TLDR
A molecular model of the retinal-binding site of rhodopsin is proposed that illustrates the specific interaction between Gly121 and the C9 methyl group of 11-cis-retinal. Expand
The Effects of Amino Acid Replacements of Glycine 121 on Transmembrane Helix 3 of Rhodopsin*
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The replacement of Gly121 resulted in a relative reversal in the selectivity of the opsin apoprotein for reconstitution with 11-cis-retinal over all-trans- retinal in COS cell membranes and the size of the residue substituted at position 121 correlated directly to the degree of blue-shift in the λmax value of the pigment. Expand
Mechanism of activation and inactivation of opsin: role of Glu113 and Lys296.
TLDR
P pH-rate profiles for the rhodopsin-catalyzed exchange of GTPgS for GDP on transducin are established and it is evident that at least two ionizable groups in addition to Lys296 and Glu113 control the formation of the active opsin state. Expand
Constitutive activation of opsin: interaction of mutants with rhodopsin kinase and arrestin.
TLDR
It is shown here that the mutants not only constitutively activate transducin but are also constitUTively activated for phosphorylation by rhodopsin kinase, suggesting that degeneration of photoreceptor cells in retinitis pigmentosa results indirectly from the activated state of the receptor, perhaps as a consequence of phosphorylated and persistent binding of arrestin. Expand
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