ArticleBiophysical journal2014
Two classes of cholesterol binding sites for the β2AR revealed by thermostability and NMR.
Article in Biophysical journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 64 citations in OpenAlex.
- Unraveling allosteric signaling of G protein-coupled receptors (GPCRs) by single-molecule fluorescence.Biophysical reviews · 2026Review
- Human class B1 GPCR modulation by plasma membrane lipids.Communications biology · 2026Article
- Conformational Heterogeneity Underlying Divergent Signaling in Class A G Protein-Coupled Receptors.ACS pharmacology & translational science · 2025Review
- Effects of Membrane Cholesterol on the Structure and Function of Selected Class A GPCRs─Challenges and Future Perspectives.Biochemistry · 2025Review
- The influence of lipids and biological membranes on the conformational equilibria of GPCRs: Insights from NMR spectroscopy.Current opinion in structural biology · 2025Review
- Solid-state NMR of membrane peptides and proteins in the lipid cubic phase.Biophysical journal · 2025Article
- Cholesterol inhibits assembly and oncogenic activation of the EphA2 receptor.Communications biology · 2025Article
- Cholesterol inhibits assembly and activation of the EphA2 receptor.bioRxiv : the preprint server for biology · 2024Article
- The mechanism of 25-hydroxycholesterol-mediated suppression of atrial β1-adrenergic responses.Pflugers Archiv : European journal of physiology · 2024Article
- Alchemical Free Energy Calculations on Membrane-Associated Proteins.Journal of chemical theory and computation · 2023Review
- Illuminating GPCR signaling mechanisms by NMR spectroscopy with stable-isotope labeled receptors.Current opinion in pharmacology · 2023Review
- Dual mechanisms of cholesterol-GPCR interactions that depend on membrane phospholipid composition.Structure (London, England : 1993) · 2023Article
- Docking cholesterol to integral membrane proteins with Rosetta.PLoS computational biology · 2023Article
- An NMR Study on Hydration and Molecular Interaction of Phytantriol-Based Liquid Crystals.Pharmaceutics · 2022Article
- A cholesterol analog stabilizes the human βScience signaling · 2022Article
- Article
- Thermostability-based binding assays reveal complex interplay of cation, substrate and lipid binding in the bacterial DASS transporter, VcINDY.The Biochemical journal · 2021Article
- Relative Affinities of Protein-Cholesterol Interactions from Equilibrium Molecular Dynamics Simulations.Journal of chemical theory and computation · 2021Article
- Allosteric Modulation of GPCRs of Class A by Cholesterol.International journal of molecular sciences · 2021Review
- Structure and Dynamics of GPCRs in Lipid Membranes: Physical Principles and Experimental Approaches.Molecules (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
Abstract
Cholesterol binding to G protein-coupled receptors (GPCRs) and modulation of their activities in membranes is a fundamental issue for understanding their function. Despite the identification of cholesterol binding sites in high-resolution x-ray structures of the ?2 adrenergic receptor (β2AR) and other GPCRs, the binding affinity of cholesterol for this receptor and exchange rates between the free and bound cholesterol remain unknown. In this study we report the existence of two classes of cholesterol binding sites in β2AR. By analyzing the β2AR unfolding temperature in lipidic cubic phase (LCP) as a function of cholesterol concentration we observed high-affinity cooperative binding of cholesterol with sub-nM affinity constant. In contrast, saturation transfer difference (STD) NMR experiments revealed the existence of a second class of cholesterol binding sites, in fast exchange on the STD NMR timescale. Titration of the STD signal as a function of cholesterol concentration provided a lower limit of 100 mM for their dissociation constant. However, these binding sites are specific for both cholesterol and β2AR, as shown with control experiments using ergosterol and a control membrane protein (KpOmpA). We postulate that this specificity is mediated by the high-affinity bound cholesterol molecules and propose the formation of transient cholesterol clusters around the high-affinity binding sites.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.