PMID:8643442

Citation	Liu, X, Garriga, P and Khorana, HG (1996) Structure and function in rhodopsin: correct folding and misfolding in two point mutants in the intradiscal domain of rhodopsin identified in retinitis pigmentosa. Proc. Natl. Acad. Sci. U.S.A. 93:4554-9
Abstract	The rhodopsin mutants P23H and G188R, identified in autosomal dominant retinitis pigmentosa (ADRP), and the site-specific mutants D190A and DeltaY191-Y192 were expressed in COS cells from synthetic mutant opsin genes containing these mutations. The proteins expressed from P23H and D190A partially regenerated the rhodopsin chromophore with 11-cis-retinal and were mixtures of the correctly folded (retinal-binding) and misfolded (non-retinal-binding) opsins. The mixtures were separated into pure, correctly folded mutant rhodopsins and misfolded opsins. The proteins expressed from the ADRP mutant G188R and the mutant DeltaY191-Y192 were composed of totally misfolded non-retinal-binding opsins. Far-UV CD spectra showed that the correctly folded mutant rhodopsins had helical content similar to that of the wild-type rhodopsin, whereas the misfolded opsins had helical content 50-70% of the wild type. The near-UV CD spectra of the misfolded mutant proteins lack the characteristic band pattern seen in the wild-type opsin, indicative of a different tertiary structure. Further, whereas the folded mutant rhodopsins were essentially resistant to trypsin digestion, the misfolded opsins were degraded to small fragments under the same conditions. Therefore, the misfolded opsins appear to be less compact in their structures than the correctly folded forms. We suggest that most, if not all, of the point mutations in the intradiscal domain identified in ADRP cause partial or complete misfolding of rhodopsin.
Links	PubMed PMC39315
Keywords	Amino Acid Sequence; Animals; Cattle; Cell Line; Gene Expression; Genes, Dominant; Humans; Molecular Sequence Data; Molecular Structure; Point Mutation; Protein Folding; Protein Structure, Secondary; Recombinant Proteins/chemistry; Recombinant Proteins/genetics; Retinitis Pigmentosa/genetics; Retinitis Pigmentosa/metabolism; Rhodopsin/chemistry; Rhodopsin/genetics; Rhodopsin/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:OPSD		GO:0071482: cellular response to light stimulus	ECO:0000315:		P		Comparisons between the mutant, incorrectly folded Rhodopsin and the correctly folded Rhodopsin resulted in a negative influence on the ability to interpret a light stimulus.	complete CACAO 9366

References

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