The steroid cholesterol is an essential component of eukaryotic membranes, and it functionally modulates membrane proteins, including G protein-coupled receptors. To reveal insight into how cholesterol modulates G protein-coupled receptors, we have used dynamic single-molecule force spectroscopy to quantify the mechanical strength and flexibility, conformational variability, and kinetic and energetic stability of structural segments stabilizing the human β2-adrenergic receptor (β2AR) in the absence and presence of the cholesterol analog cholesteryl hemisuccinate (CHS). CHS considerably increased the kinetic, energetic, and mechanical stability of almost every structural segment at sufficient magnitude to alter the structure and functional relationship of β2AR. One exception was the structural core segment of β2AR, which establishes multiple ligand binding sites, and its properties were not significantly influenced by CHS.
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Publication status||Published - 11 Dec 2012|
- Atomic force microscopy
- Energy landscape
- Intermolecular and intramolecular interactions