The Morphology and Composition of Cholesterol-Rich Micellar Nanostructures Determine Transmembrane Protein (GPCR) Activity

Biophys J. 2011 Jan 19;100(2):L11-3. doi: 10.1016/j.bpj.2010.12.3698.

Abstract

We examined model mixed micelles consisting of the nonionic surfactant n-dodecyl-β-D-maltoside, 3-(3-cholamidopropyl)-dimethylammoniopropane sulfonate, and the cholesterol derivative cholesteryl hemisuccinate (CHS) to identify micellar properties that are correlated with the in vitro conformational stability and activity of the human adenosine A₂a receptor, a G-protein coupled receptor. Small-angle neutron scattering was used to determine micellar structure and composition as a function of concentration of the various components, and radioligand binding was used as a sensitive probe for receptor activity. Micelles adopted an oblate ellipsoidal morphology and exhibited a reduction in size and change in curvature upon addition of CHS. Our results show a strong correlation between the number of CHS monomers per micelle and the activity of the receptor reconstituted in those micelles. Micelles that yield optimal human adenosine A₂a receptor stability closely mimic the cholesterol composition and thickness of mammalian membranes. Thus, successful reconstitution of the receptor is dependent on both specific lipid-protein interactions and the geometry of the micelle environment.

Publication types

  • Letter

MeSH terms

  • Cholesterol / chemistry*
  • Cholesterol Esters / chemistry*
  • Cholic Acids / chemistry
  • Glucosides / chemistry*
  • Humans
  • Membrane Proteins / ultrastructure
  • Micelles*
  • Molecular Conformation
  • Nanostructures / ultrastructure
  • Protein Transport / physiology*
  • Receptors, G-Protein-Coupled / chemistry*
  • Receptors, G-Protein-Coupled / metabolism*
  • Scattering, Small Angle
  • Surface Properties

Substances

  • Cholesterol Esters
  • Cholic Acids
  • Glucosides
  • Membrane Proteins
  • Micelles
  • Receptors, G-Protein-Coupled
  • dodecyl maltoside
  • Cholesterol
  • 3-((3-cholamidopropyl)dimethylammonium)-1-propanesulfonate
  • cholesteryl succinate