ArticleThe Journal of biological chemistry2013
Thermal stability of rhodopsin and progression of retinitis pigmentosa: comparison of S186W and D190N rhodopsin mutants.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- Stabilizing effects of geraniol on native and pathogenic M39R rhodopsin variants.Frontiers in neuroscience · 2026Article
- Genetic Therapies for Retinitis Pigmentosa: Current Breakthroughs and Future Directions.Journal of clinical medicine · 2025Review
- Structural basis for the allosteric modulation of rhodopsin by nanobody binding to its extracellular domain.Nature communications · 2023Article
- Effect of Trace Metal Ions on the Conformational Stability of the Visual Photoreceptor Rhodopsin.International journal of molecular sciences · 2023Article
- Long-term vitamin A supplementation in a preclinical mouse model for RhoD190N-associated retinitis pigmentosa.Human molecular genetics · 2022Article
- Genetic dissection of non-syndromic retinitis pigmentosa.Indian journal of ophthalmology · 2022Review
- Effect of Sodium Valproate on the Conformational Stability of the Visual G Protein-Coupled Receptor Rhodopsin.Molecules (Basel, Switzerland) · 2021Article
- Dark noise and retinal degeneration from D190N-rhodopsin.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Mechanisms of neurodegeneration in a preclinical autosomal dominant retinitis pigmentosa knock-in model with a RhoCellular and molecular life sciences : CMLS · 2019Article
- Molecular mechanism for thermal denaturation of thermophilic rhodopsin.Chemical science · 2019Article
- Characterizing variants of unknown significance in rhodopsin: A functional genomics approach.Human mutation · 2019Article
- Coupling of Human Rhodopsin to a Yeast Signaling Pathway Enables Characterization of Mutations Associated with Retinal Disease.Genetics · 2019Article
- Clustered Regularly Interspaced Short Palindromic Repeats-Based Genome Surgery for the Treatment of Autosomal Dominant Retinitis Pigmentosa.Ophthalmology · 2018Article
- Protein Sequence and Membrane Lipid Roles in the Activation Kinetics of Bovine and Human Rhodopsins.Biophysical journal · 2017Article
- Flavonoid allosteric modulation of mutated visual rhodopsin associated with retinitis pigmentosa.Scientific reports · 2017Article
- Structural role of the T94I rhodopsin mutation in congenital stationary night blindness.EMBO reports · 2016Article
- Unusual kinetics of thermal decay of dim-light photoreceptors in vertebrate vision.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Constitutively active rhodopsin and retinal disease.Advances in pharmacology (San Diego, Calif.) · 2014Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Over 100 point mutations in the rhodopsin gene have been associated with retinitis pigmentosa (RP), a family of inherited visual disorders. Among these, we focused on characterizing the S186W mutation. We compared the thermal properties of the S186W mutant with another RP-causing mutant, D190N, and with WT rhodopsin. To assess thermal stability, we measured the rate of two thermal reactions contributing to the thermal decay of rhodopsin as follows: thermal isomerization of 11-cis-retinal and hydrolysis of the protonated Schiff base linkage between the 11-cis-retinal chromophore and opsin protein. We used UV-visible spectroscopy and HPLC to examine the kinetics of these reactions at 37 and 55 °C for WT and mutant rhodopsin purified from HEK293 cells. Compared with WT rhodopsin and the D190N mutant, the S186W mutation dramatically increases the rates of both thermal isomerization and dark state hydrolysis of the Schiff base by 1-2 orders of magnitude. The results suggest that the S186W mutant thermally destabilizes rhodopsin by disrupting a hydrogen bond network at the receptor's active site. The decrease in the thermal stability of dark state rhodopsin is likely to be associated with higher levels of dark noise that undermine the sensitivity of rhodopsin, potentially accounting for night blindness in the early stages of RP. Further studies of the thermal stability of additional pathogenic rhodopsin mutations in conjunction with clinical studies are expected to provide insight into the molecular mechanism of RP and test the correlation between rhodopsin's thermal stability and RP progression in patients.
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