Dimerization of β2-adrenergic receptor is responsible for the constitutive activity subjected to inverse agonism
SCIE
SCOPUS
- Title
- Dimerization of β2-adrenergic receptor is responsible for the constitutive activity subjected to inverse agonism
- Authors
- Kwon, Yonghoon; Kim, Do-Hyeon; Jeong, Min Gyu; Hong, Minh-Triet; Park, Soyeon; Chang, Yeonho; Zhou, Kai; Park, Seung-Yeol; Zhang, Jin; Ryu, Sung Ho
- Date Issued
- 2022-10
- Publisher
- Elsevier Inc.
- Abstract
- Dimerization of beta 2-adrenergic receptor (β2-AR) has been observed across various physiologies. However, the function of dimeric β2-AR is still elusive. Here, we revealed that dimerization of β2-AR is responsible for the constitutive activity of β2-AR generating inverse agonism. Using a co-immunoimmobilization assay, we found that transient β2-AR dimers exist in a resting state, and the dimer was disrupted by the inverse agonists. A Gαs preferentially interacts with dimeric β2-AR, but not monomeric β2-AR, in a resting state, resulting in the production of a resting cAMP level. The formation of β2-AR dimers requires cholesterol on the plasma membrane. The cholesterol did not interfere with the agonist-induced activation of monomeric β2-AR, unlike the inverse agonists, implying that the cholesterol is a specific factor regulating the dimerization of β2-AR. Our model not only shows the function of dimeric β2-AR but also provides a molecular insight into the mechanism of the inverse agonism of β2-AR.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/114016
- DOI
- 10.1016/j.chembiol.2022.09.001
- ISSN
- 2451-9448
- Article Type
- Article
- Citation
- Cell Chemical Biology, vol. 29, no. 10, page. 1532 - +, 2022-10
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