June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Modulation of the acylation of the C-terminal segment of GRK1 drastically influences its solubility and membrane-binding properties
Author Affiliations & Notes
  • Marc-Antoine Millette
    Universite Laval, Quebec, Quebec, Canada
  • Camille Gagnon
    Universite Laval, Quebec, Quebec, Canada
  • Christian Salesse
    Universite Laval, Quebec, Quebec, Canada
  • Footnotes
    Commercial Relationships   Marc-Antoine Millette, None; Camille Gagnon, None; Christian Salesse, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 1575. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Marc-Antoine Millette, Camille Gagnon, Christian Salesse; Modulation of the acylation of the C-terminal segment of GRK1 drastically influences its solubility and membrane-binding properties. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1575.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

  • Supplements

Purpose : G-protein coupled receptors (GPCR) are key receptors in signal transduction. They are inactivated by G-protein coupled receptor kinases (GRK). GRK1 is the first member of the GRK family, which includes seven members. All GRK bind membranes via their C-terminal segment. Four GRKs are acylated at their C-terminus: GRK1 is farnesylated, GRK7 is geranylgeranylated, GRK4 and 6 are palmitoylated. The objective of this research work was to compare the extent of membrane binding of the 30 most C-terminus amino acid residues of GRK1 bearing three different acyl groups (palmitoyl, farnesyl and geranylgeranyl).

Methods : Infrared spectroscopy and circular dichroism measurements were performed to determine the secondary structure of the C-terminal segments. Fluorescence spectroscopy measurements were performed to gather information on the environment of tryptophan 531.

Results : Infrared and circular dichroism measurements showed these the acylated C-terminal segments adopt a random coil structure. Intrinsic fluorescence measurements suggest that the farnesylated segment of GRK1 is soluble in aqueous solution, whereas the palmitoylated segment is only partially soluble and the geranylgeranylated segment is aggregated. In addition, no significant increase in the fluorescence of the farnesylated segment was observed in the presence of sodium dodecyl sulfate (SDS). Moreover, measurements at increasing concentration of small unilamellar vesicles (SUVs) made of palmitoyl-oleoyl-phosphocholine (POPC) showed little modification in the position of the emission maximum, suggesting that this residue is not membrane embedded. In contrast, a drastic increase in fluorescence of the palmitoylated segment was observed in presence of SDS and SUVs, whereas an increase was only observed with SDS for the geranylgeranylated segment. Membrane binding to phospholipid monolayers shows a preferential binding of the farnesylated segment to unsaturated phospholipids, whereas a higher affinity to saturated phospholipids was observed for the palmitoylated segment.

Conclusions : The modification of the acylation of the C-terminal segment of GRK1 using either a farnesyl, a palmitoyl or a geranylgeranyl group drastically lowered its solubility. The preferential binding of the farnesylated segment for unsaturated phospholipids was modified in favor of saturated phospholipids with the palmitoylated segment.

This is a 2021 ARVO Annual Meeting abstract.


This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.