Cholesterol increases kinetic, energetic, and mechanical stability of the human β2-adrenergic receptor
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Cholesterol increases kinetic, energetic, and mechanical stability of the human β2-adrenergic receptor. / Zocher, Michael; Zhang, Cheng; Rasmussen, Søren Gøgsig Faarup; Kobilka, Brian K; Müller, Daniel J.
I: Proceedings of the National Academy of Sciences of the United States of America, Bind 109, Nr. 50, 11.12.2012, s. E3463–E3472.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Cholesterol increases kinetic, energetic, and mechanical stability of the human β2-adrenergic receptor
AU - Zocher, Michael
AU - Zhang, Cheng
AU - Rasmussen, Søren Gøgsig Faarup
AU - Kobilka, Brian K
AU - Müller, Daniel J
PY - 2012/12/11
Y1 - 2012/12/11
N2 - 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.
AB - 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.
KW - Animals
KW - Biomechanical Phenomena
KW - Cholesterol Esters
KW - Energy Metabolism
KW - Humans
KW - Kinetics
KW - Microscopy, Atomic Force
KW - Models, Molecular
KW - Protein Conformation
KW - Protein Interaction Mapping
KW - Protein Stability
KW - Proteolipids
KW - Receptors, Adrenergic, beta-2
KW - Recombinant Proteins
KW - Sf9 Cells
KW - Spodoptera
KW - Unfolded Protein Response
U2 - 10.1073/pnas.1210373109
DO - 10.1073/pnas.1210373109
M3 - Journal article
C2 - 23151510
VL - 109
SP - E3463–E3472
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 50
ER -
ID: 120587456