Docosahexaenoic acid phospholipid differentially modulates the conformation of G90V and N55K rhodopsin mutants associated with retinitis pigmentosa

• Published in: Biochimica et biophysica acta. Biomembranes 2017-05, Vol.1859 (5), p.975-981
• Main Authors: Dong, Xiaoyun, Herrera-Hernández, María Guadalupe, Ramon, Eva, Garriga, Pere
• Format: Article
• Language: English
• Subjects: Animals; Artificial membranes; Cercopithecus aethiops; COS Cells; Degeneració retinal; Docosahexaenoic Acids - chemistry; Enginyeria química; Lipid-protein interactions; Liposomes - chemistry; Mutation; Phosphorylcholine - chemistry; Protein Conformation; Protein Stability; Proteins; Proteïnes; Receptor stability; Retinal degeneration; Retinitis Pigmentosa - etiology; Rhodopsin; Rhodopsin - chemistry; Spectrometry, Fluorescence; Spectrophotometry, Ultraviolet; Trastorns de la visió; Àrees temàtiques de la UPC
• ISSN: 0005-2736; 1879-2642; 1879-2642
• DOI: 10.1016/j.bbamem.2017.02.006

Rhodopsin is the visual photoreceptor of the retinal rod cells that mediates dim light vision and a prototypical member of the G protein-coupled receptor superfamily. The structural stability and functional performance of rhodopsin are modulated by membrane lipids. Docosahexaenoic acid has been shown to interact with native rhodopsin but no direct evidence has been established on the effect of such lipid on the stability and regeneration of rhodopsin mutants associated with retinal diseases. The stability and regeneration of two thermosensitive mutants G90V and N55K, associated with the retinal degenerative disease retinitis pigmentosa, have been analyzed in docosohexaenoic phospholipid (1,2-didocosa-hexaenoyl-sn-glycero-3-phosphocholine; DDHA-PC) liposomes. G90V mutant reconstituted in DDHA-PC liposomes significantly increased its thermal stability, but N55K mutant showed similar thermal sensitivity both in dodecyl maltoside detergent solution and in DDHA-PC liposomes. The retinal release process, measured by fluorescence spectroscopy, became faster in the lipid system for the two mutants. The opsin conformation was stabilized for the G90V mutant allowing improved retinal uptake whereas no chromophore binding could be detected for N55K opsin after photoactivation. The results emphasize the distinct role of DHA on different phenotypic rhodopsin mutations associated with classical (G90V) and sector (N55K) retinitis pigmentosa. [Display omitted] •DDHA-PC liposomes stabilize the G90V rhodopsin mutation.•The liposome system allows retinal binding only for G90V but not for N55K mutant.•G90V conformation is likely stabilized by interaction with DHA fatty acid.•DDHA-PC effects on rhodopsin mutants associated with different RP clinical phenotypes