Altered functionality in rhodopsin point mutants associated with retinitis pigmentosa

Anna Andrés, Pere Garriga, Joan Manyosa

Research output: Contribution to journalArticleResearchpeer-review

129 Citations (Scopus)

Abstract

Point mutations found in rhodopsin associated with the retinal degenerative disease retinitis pigmentosa have been expressed in mammalian COS-1 cells, purified, and characterised. The mutations characterised - most of them for the first time - have been Met44Thr, Gly114Asp, Arg135Leu, Val137Met, and Pro171Leu in the transmembrane domain; Leu328Pro and Ala346Pro in the C-terminal tail of the cytoplasmic domain; and Gly106Trp in the intradiscal domain. Several of these mutations cause misfolding which results in impaired 11-cis-retinal binding. Two of them, Met44Thr and Val137Met, show spectral and structural features similar to those of wild type rhodopsin (Type I mutants) but significantly increased transducin initial activation rates. We propose that, in the case of these mutants, abnormal functioning resulting in faster activation kinetics could also play a role in retinitis pigmentosa by altering the stoichiometric balance of the different proteins involved in the phototransduction biochemical reactions. © 2003 Elsevier Science (USA). All rights reserved.
Original languageEnglish
Pages (from-to)294-301
JournalBiochem. biophys. res. commun.
Volume303
Issue number1
DOIs
Publication statusPublished - 28 Mar 2003

Keywords

  • G-protein-coupled receptor
  • Protein misfolding
  • Retinitis pigmentosa
  • Transducin activation

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