Comparison of the molecular properties of retinitis pigmentosa P23H and N15S amino acid replacements in rhodopsin
| Autor: | Joan Planas-Iglesias, Harpreet Kaur Dhiman, Judith Klein-Seetharaman, Alessandro Iannaccone, Naveena Yanamala, Fernanda Balem, Julian Ollesch, Kalyan C. Tirupula, Barbara J. Jennings, Klaus Gerwert, James Mitchell, David Man |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Retinal degeneration Protein Structure Comparison Circular dichroism Glycosylation genetic structures Glycobiology Thermal Stability Biochemistry 0302 clinical medicine Protein structure Macromolecular Structure Analysis Medicine and Health Sciences Post-Translational Modification Amino Acids Peptide sequence Materials Multidisciplinary biology Chemistry Organic Compounds Physics Monomers Rhodopsin Physical Sciences Medicine Thermodynamics Retinal Disorders Protein folding Retinitis Pigmentosa Research Article Protein Structure Science Materials Science 03 medical and health sciences Retinitis pigmentosa medicine Genetics Point Mutation Dimers Molecular Biology Point mutation Organic Chemistry Retinitis Chemical Compounds Biology and Life Sciences Proteins medicine.disease Polymer Chemistry Ophthalmology 030104 developmental biology Amino Acid Substitution Oligomers Mutation Biophysics biology.protein sense organs 030217 neurology & neurosurgery |
| Zdroj: | PLoS ONE PLoS ONE, Vol 14, Iss 5, p e0214639 (2019) |
| ISSN: | 1932-6203 |
| Popis: | Mutations in the RHO gene encoding for the visual pigment protein, rhodopsin, are among the most common cause of autosomal dominant retinitis pigmentosa (ADRP). Previous studies of ADRP mutations in different domains of rhodopsin have indicated that changes that lead to more instability in rhodopsin structure are responsible for more severe disease in patients. Here, we further test this hypothesis by comparing side-by-side and therefore quantitatively two RHO mutations, N15S and P23H, both located in the N-terminal intradiscal domain. The in vitro biochemical properties of these two rhodopsin proteins, expressed in stably transfected tetracycline-inducible HEK293S cells, their UV-visible absorption, their Fourier transform infrared, circular dichroism and Metarhodopsin II fluorescence spectroscopy properties were characterized. As compared to the severely impaired P23H molecular function, N15S is only slightly defective in structure and stability. We propose that the molecular basis for these structural differences lies in the greater distance of the N15 residue as compared to P23 with respect to the predicted rhodopsin folding core. As described previously for WT rhodopsin, addition of the cytoplasmic allosteric modulator chlorin e6 stabilizes especially the P23H protein, suggesting that chlorin e6 may be generally beneficial in the rescue of those ADRP rhodopsin proteins whose stability is affected by amino acid replacement. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |