Mechanism of allosteric regulation of β2-adrenergic receptor by cholesterol
| LEADER | caa a22 4500 | ||
|---|---|---|---|
| 001 | 528785591 | ||
| 005 | 20191104030335.0 | ||
| 007 | cr unu---uuuuu | ||
| 008 | 180924e20161129xx s 000 0 eng | ||
| 024 | 7 | 0 | |a 10.3929/ethz-b-000123638 |2 doi |
| 024 | 7 | 0 | |a 10.7554/eLife.18432 |2 doi |
| 035 | |a (ETHRESEARCH)oai:www.research-collecti.ethz.ch:20.500.11850/123638 | ||
| 245 | 0 | 0 | |a Mechanism of allosteric regulation of β2-adrenergic receptor by cholesterol |h [Elektronische Daten] |c [Moutusi Manna, Miia Niemelä, Joona Tynkkynen, Matti Javanainen, Waldemar Kulig, Daniel J.; id_orcid 0000-0003-3075-0665 Müller, Tomasz Rog, Ilpo Vattulainen] |
| 506 | |a Open access |2 ethresearch | ||
| 520 | 3 | |a There is evidence that lipids can be allosteric regulators of membrane protein structure and activation. However, there are no data showing how exactly the regulation emerges from specific lipid-protein interactions. Here we show in atomistic detail how the human β2-adrenergic receptor (β2AR) - a prototypical G protein-coupled receptor - is modulated by cholesterol in an allosteric fashion. Extensive atomistic simulations show that cholesterol regulates β2AR by limiting its conformational variability. The mechanism of action is based on the binding of cholesterol at specific high-affinity sites located near the transmembrane helices 5-7 of the receptor. The alternative mechanism, where the β2AR conformation would be modulated by membrane-mediated interactions, plays only a minor role. Cholesterol analogues also bind to cholesterol binding sites and impede the structural flexibility of β2AR, however cholesterol generates the strongest effect. The results highlight the capacity of lipids to regulate the conformation of membrane receptors through specific interactions. | |
| 540 | |a Creative Commons Attribution 4.0 International |u http://creativecommons.org/licenses/by/4.0 |2 ethresearch | ||
| 700 | 1 | |a Manna |D Moutusi |e joint author | |
| 700 | 1 | |a Niemelä |D Miia |e joint author | |
| 700 | 1 | |a Tynkkynen |D Joona |e joint author | |
| 700 | 1 | |a Javanainen |D Matti |e joint author | |
| 700 | 1 | |a Kulig |D Waldemar |e joint author | |
| 700 | 1 | |a Müller |D Daniel J.; id_orcid 0000-0003-3075-0665 |e joint author | |
| 700 | 1 | |a Rog |D Tomasz |e joint author | |
| 700 | 1 | |a Vattulainen |D Ilpo |e joint author | |
| 773 | 0 | |t eLife |d Cambridge : eLife Sciences Publications |g 5, p. e18432 | |
| 856 | 4 | 0 | |u http://hdl.handle.net/20.500.11850/123638 |q text/html |z WWW-Backlink auf das Repository (Open access) |
| 908 | |D 1 |a Journal Article |2 ethresearch | ||
| 950 | |B ETHRESEARCH |P 856 |E 40 |u http://hdl.handle.net/20.500.11850/123638 |q text/html |z WWW-Backlink auf das Repository (Open access) | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Manna |D Moutusi |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Niemelä |D Miia |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Tynkkynen |D Joona |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Javanainen |D Matti |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Kulig |D Waldemar |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Müller |D Daniel J.; id_orcid 0000-0003-3075-0665 |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Rog |D Tomasz |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Vattulainen |D Ilpo |e joint author | ||
| 950 | |B ETHRESEARCH |P 773 |E 0- |t eLife |d Cambridge : eLife Sciences Publications |g 5, p. e18432 | ||
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 949 | |B ETHRESEARCH |F ETHRESEARCH |b ETHRESEARCH |j Journal Article |c Open access | ||