A phe-rich region in short-wavelength sensitive opsins is responsible for their aggregation in the absence of 11-cis-retinal

Tao Zhang, Yingbin Fu

Research output: Contribution to journalArticlepeer-review

Abstract

Human blue and mouse S-opsin are prone to aggregation in the absence of 11-cis-retinal, which underlie the rapid cone degeneration in human patients and animal models of Leber congenital amaurosis (LCA). By in silico analysis and domain swapping experiments, we show that a Phe-rich region in short-wavelength sensitive (SWS) opsins, but not in medium/long-wavelength sensitive opsins, is responsible for SWS opsin aggregation. Mutagenesis studies suggest that Phe residues in this region are critical in mediating protein aggregation. Fusing the Phe-rich region of SWS opsins to GFP causes the latter to aggregate. Our findings suggest that new therapeutics can be designed to disrupt the Phe-rich region in preventing cone degeneration due to S-opsin aggregation in LCA.

Original languageEnglish (US)
Pages (from-to)2430-2434
Number of pages5
JournalFEBS Letters
Volume587
Issue number15
DOIs
StatePublished - Aug 2 2013
Externally publishedYes

Keywords

  • Cone degeneration
  • G-protein-coupled receptors (GPCRs)
  • Leber congenital amaurosis (LCA)
  • Medium/long-wavelength sensitive opsins (M/LWS)
  • Opsin aggregation
  • RPE65 LRAT
  • Short-wavelength sensitive opsins (SWS)

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Structural Biology

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