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FEBS Lett. 2015 Oct 7;589(20 Pt B):3119-25. doi: 10.1016/j.febslet.2015.08.042. Epub 2015 Sep 7.

Misfolded opsin mutants display elevated β-sheet structure.

Author information

1
National Synchrotron Light Source-II, Brookhaven National Laboratory, Upton, NY 11973, USA. Electronic address: lmiller@bnl.gov.
2
Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH 44106, USA; Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195, USA.
3
Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH 44106, USA.
4
Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH 44106, USA; Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195, USA. Electronic address: paul.park@case.edu.

Abstract

Mutations in rhodopsin can cause misfolding and aggregation of the receptor, which leads to retinitis pigmentosa, a progressive retinal degenerative disease. The structure adopted by misfolded opsin mutants and the associated cell toxicity is poorly understood. Förster resonance energy transfer (FRET) and Fourier transform infrared (FTIR) microspectroscopy were utilized to probe within cells the structures formed by G188R and P23H opsins, which are misfolding mutants that cause autosomal dominant retinitis pigmentosa. Both mutants formed aggregates in the endoplasmic reticulum and exhibited altered secondary structure with elevated β-sheet and reduced α-helical content. The newly formed β-sheet structure may facilitate the aggregation of misfolded opsin mutants. The effects observed for the mutants were unrelated to retention of opsin molecules in the endoplasmic reticulum itself.

KEYWORDS:

G protein-coupled receptor; Membrane protein; Protein aggregation; Protein misfolding; Retinal degeneration; Secondary structure

PMID:
26358292
PMCID:
PMC4641566
DOI:
10.1016/j.febslet.2015.08.042
[Indexed for MEDLINE]
Free PMC Article

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