Phosphatidylethanolamine enhances rhodopsin photoactivation and transducin binding in a solid supported lipid bilayer as determined using plasmon-waveguide resonance spectroscopy

Biophys J. 2005 Jan;88(1):198-210. doi: 10.1529/biophysj.104.046722. Epub 2004 Oct 22.

Abstract

Flash photolysis studies have shown that the membrane lipid environment strongly influences the ability of rhodopsin to form the key metarhodopsin II intermediate. Here we have used plasmon-waveguide resonance (PWR) spectroscopy, an optical method sensitive to both mass and conformation, to probe the effects of lipid composition on conformational changes of rhodopsin induced by light and due to binding and activation of transducin (G(t)). Octylglucoside-solubilized rhodopsin was incorporated by detergent dilution into solid-supported bilayers composed either of egg phosphatidylcholine or various mixtures of a nonlamellar-forming lipid (dioleoylphosphatidylethanolamine; DOPE) together with a lamellar-forming lipid (dioleoylphosphatidylcholine; DOPC). Light-induced proteolipid conformational changes as a function of pH correlated well with previous flash photolysis studies, indicating that the PWR spectral shifts monitored metarhodopsin II formation. The magnitude of these effects, and hence the extent of the conformational transition, was found to be proportional to the DOPE content. Our data are consistent with previous suggestions that lipids having a negative spontaneous curvature favor elongation of rhodopsin during the activation process. In addition, measurements of the G(t)/rhodopsin interaction in a DOPC/DOPE (25:75) bilayer at pH 5 demonstrated that light activation increased the affinity for G(t) from 64 nM to 0.7 nM, whereas G(t) affinity for dark-adapted rhodopsin was unchanged. By contrast, in DOPC bilayers the affinity of G(t) for light-activated rhodopsin was only 18 nM at pH 5. Moreover exchange of GDP for GTP gamma S was also monitored by PWR spectroscopy. Only the light-activated receptor was able to induce this exchange which was unaffected by DOPE incorporation. These findings demonstrate that nonbilayer-forming lipids can alter functionally linked conformational changes of G-protein-coupled receptors in membranes, as well as their interactions with downstream effector proteins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biophysical Phenomena
  • Biophysics
  • Cattle
  • Cell Membrane / metabolism
  • Detergents / pharmacology
  • Glucosides / pharmacology
  • Guanosine 5'-O-(3-Thiotriphosphate) / chemistry
  • Hydrogen-Ion Concentration
  • Light
  • Lipid Bilayers / chemistry
  • Lipids / chemistry
  • Phosphatidylcholines / chemistry
  • Phosphatidylethanolamines / chemistry
  • Phosphatidylethanolamines / pharmacology*
  • Protein Binding
  • Protein Conformation
  • Retinal Rod Photoreceptor Cells / metabolism
  • Rhodopsin / chemistry*
  • Spectrophotometry
  • Time Factors
  • Transducin / chemistry*

Substances

  • 1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine
  • Detergents
  • Glucosides
  • Lipid Bilayers
  • Lipids
  • Phosphatidylcholines
  • Phosphatidylethanolamines
  • octyl-beta-D-glucoside
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • phosphatidylethanolamine
  • Rhodopsin
  • Transducin
  • 1,2-oleoylphosphatidylcholine