Abstract:
: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 β(2)-adrenergic receptor (β(2)AR) 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 β(2)AR. One exception was the structural core segment of β(2)AR, which establishes multiple ligand binding sites, and its properties were not significantly influenced by CHS.
journal_name
Proc Natl Acad Sci U S Aauthors
Zocher M,Zhang C,Rasmussen SG,Kobilka BK,Müller DJdoi
10.1073/pnas.1210373109subject
Has Abstractpub_date
2012-12-11 00:00:00pages
E3463-72issue
50eissn
0027-8424issn
1091-6490pii
1210373109journal_volume
109pub_type
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