ArticleStructure (London, England : 1993)2009
A role for a specific cholesterol interaction in stabilizing the Apo configuration of the human A(2A) adenosine receptor.
Article in Structure (London, England : 1993), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
53 citing papers in PubMed, 118 citations in OpenAlex.
- Effects of Membrane Cholesterol on the Structure and Function of Selected Class A GPCRs─Challenges and Future Perspectives.Biochemistry · 2025Review
- Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery.Nature reviews. Drug discovery · 2025Review
- Parsing Dynamics of Protein Backbone NH and Side-Chain Methyl Groups using Molecular Dynamics Simulations.Journal of chemical theory and computation · 2024Article
- Improved Highly Mobile Membrane Mimetic Model for Investigating Protein-Cholesterol Interactions.Journal of chemical information and modeling · 2024Article
- N-substituted tetrahydro-beta-carboline as mu-opioid receptors ligands: in silico study; molecular docking, ADMET and molecular dynamics approach.Molecular diversity · 2024Article
- Novel Inhibitors to MmpL3 Transporter ofACS omega · 2024Article
- How Neuromembrane Lipids Modulate Membrane Proteins: Insights from G-Protein-Coupled Receptors (GPCRs) and Receptor Tyrosine Kinases (RTKs).Cold Spring Harbor perspectives in biology · 2023Review
- Article
- Inhibition Mechanism of Anti-TB Drug SQ109: Allosteric Inhibition of TMM Translocation of Mycobacterium Tuberculosis MmpL3 Transporter.Journal of chemical information and modeling · 2023Article
- Molecular Biophysics of Class A G Protein Coupled Receptors-Lipids Interactome at a Glance-Highlights from the ABiomolecules · 2023Review
- Potential antiviral peptides against the nucleoprotein of SARS-CoV-2.Chemicke zvesti · 2023Article
- Lysine 101 in the CRAC Motif in Transmembrane Helix 2 Confers Cholesterol-Induced Thermal Stability to the SerotoninThe Journal of membrane biology · 2022Article
- Cholesterol Dependent Activity of the Adenosine AMolecules (Basel, Switzerland) · 2022Article
- Structure-Activity Relationship Studies on Oxazolo[3,4-Journal of medicinal chemistry · 2021Article
- Clinical HDAC Inhibitors Are Effective Drugs to Prevent the Entry of SARS-CoV2.ACS pharmacology & translational science · 2020Article
- Binding Mode Exploration of B1 Receptor Antagonists' by the Use of Molecular Dynamics and Docking Simulation-How Different Target Engagement Can Determine Different Biological Effects.International journal of molecular sciences · 2020Article
- In Silico Drug Design for Purinergic GPCRs: Overview on Molecular Dynamics Applied to Adenosine and P2Y Receptors.Biomolecules · 2020Review
- Insights into adenosine A2A receptor activation through cooperative modulation of agonist and allosteric lipid interactions.PLoS computational biology · 2020Article
- Computer simulations of protein-membrane systems.Progress in molecular biology and translational science · 2020Article
- Emerging Diversity in Lipid-Protein Interactions.Chemical reviews · 2019Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The function of G-protein-coupled receptors is tightly modulated by the lipid environment. Long-timescale molecular dynamics simulations (totaling approximately 3 mus) of the A(2A) receptor in cholesterol-free bilayers, with and without the antagonist ZM241385 bound, demonstrate the instability of helix II in the apo receptor in cholesterol-poor membrane regions. We directly observe that the effect of cholesterol binding is to stabilize helix II against a buckling-type deformation, perhaps rationalizing the observation that the A(2A) receptor couples to G protein only in the presence of cholesterol (Zezula and Freissmuth, 2008). The results suggest a mechanism by which the A(2A) receptor may function as a coincidence detector, activating only in the presence of both cholesterol and agonist. We also observed a previously hypothesized conformation of the tryptophan "rotameric switch" on helix VI in which a phenylalanine on helix V positions the tryptophan out of the ligand binding pocket.
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Registered trials
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.