A cholesterol analog stabilizes the human β2-adrenergic receptor nonlinearly with temperature

Tetiana Serdiuk, Moutusi Manna, Cheng Zhang, Stefania A. Mari, Waldemar Kulig, Kristyna Pluhackova, Brian K. Kobilka, Ilpo Vattulainen, Daniel J. Müller

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Abstract

In cell membranes, G protein-coupled receptors (GPCRs) interact with cholesterol, which modulates their assembly, stability, and conformation. Previous studies have shown how cholesterol modulates the structural properties of GPCRs at ambient temperature. Here, we characterized the mechanical, kinetic, and energetic properties of the human β2-adrenergic receptor (β2AR) in the presence and absence of the cholesterol analog cholesteryl hemisuccinate (CHS) at room temperature (25°C), at physiological temperature (37°C), and at high temperature (42°C). We found that CHS stabilized various structural regions of β2AR differentially, which changed nonlinearly with temperature. Thereby, the strongest effects were observed for structural regions that are important for receptor signaling. Moreover, at 37°C, but not at 25° or 42°C, CHS caused β2AR to increase and stabilize conformational substates to adopt to basal activity. These findings indicate that the nonlinear, temperature-dependent action of CHS in modulating the structural and functional properties of this GPCR is optimized for 37°C.

Original languageEnglish
Article numbereabi7031
Number of pages12
JournalScience Signaling
Volume15
Issue number737
DOIs
Publication statusPublished - 7 Jun 2022
Publication typeA1 Journal article-refereed

Publication forum classification

  • Publication forum level 2

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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