ArticleProteins2009
Structural and dynamic effects of cholesterol at preferred sites of interaction with rhodopsin identified from microsecond length molecular dynamics simulations.
Article in Proteins, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 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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Who cites it
50 citing papers in PubMed, 91 citations in OpenAlex.
- Effects of Membrane Cholesterol on the Structure and Function of Selected Class A GPCRs─Challenges and Future Perspectives.Biochemistry · 2025Review
- Small-Molecule Ligands of Rhodopsin and Their Therapeutic Potential in Retina Degeneration.International journal of molecular sciences · 2025Review
- Aberrant lipid accumulation and retinal pigment epithelium dysfunction in PRCD-deficient mice.Experimental eye research · 2024Article
- Improved Highly Mobile Membrane Mimetic Model for Investigating Protein-Cholesterol Interactions.Journal of chemical information and modeling · 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
- PI(4,5)PAdvances in experimental medicine and biology · 2023Article
- Lysine 101 in the CRAC Motif in Transmembrane Helix 2 Confers Cholesterol-Induced Thermal Stability to the SerotoninThe Journal of membrane biology · 2022Article
- Molecular Simulations and Drug Discovery of Adenosine Receptors.Molecules (Basel, Switzerland) · 2022Review
- PyLipID: A Python Package for Analysis of Protein-Lipid Interactions from Molecular Dynamics Simulations.Journal of chemical theory and computation · 2022Article
- Evidence that specific interactions play a role in the cholesterol sensitivity of G protein-coupled receptors.Biochimica et biophysica acta. Biomembranes · 2021Article
- Reconstruction of apo A2A receptor activation pathways reveal ligand-competent intermediates and state-dependent cholesterol hotspots.Scientific reports · 2019Article
- Characterization of Lipid-Protein Interactions and Lipid-Mediated Modulation of Membrane Protein Function through Molecular Simulation.Chemical reviews · 2019Review
- Multiscale Simulations of Biological Membranes: The Challenge To Understand Biological Phenomena in a Living Substance.Chemical reviews · 2019Article
- Emerging Diversity in Lipid-Protein Interactions.Chemical reviews · 2019Review
- Computational Modeling of Realistic Cell Membranes.Chemical reviews · 2019Review
- Interfacial Binding Sites for Cholesterol on G Protein-Coupled Receptors.Biophysical journal · 2019Article
- State-dependent Lipid Interactions with the A2a Receptor Revealed by MD Simulations Using In Vivo-Mimetic Membranes.Structure (London, England : 1993) · 2019Article
- Structural Changes Due to Antagonist Binding in Ligand Binding Pocket of Androgen Receptor Elucidated Through Molecular Dynamics Simulations.Frontiers in pharmacology · 2018Article
- Identification of Two New Cholesterol Interaction Sites on the ABiophysical journal · 2017Article
- Impact of Lipid Composition and Receptor Conformation on the Spatio-temporal Organization of μ-Opioid Receptors in a Multi-component Plasma Membrane Model.PLoS computational biology · 2016Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
An unresolved question about GPCR function is the role of membrane components in receptor stability and activation. In particular, cholesterol is known to affect the function of membrane proteins, but the details of its effect on GPCRs are still elusive. Here, we describe how cholesterol modulates the behavior of the TM1-TM2-TM7-helix 8(H8) functional network that comprises the highly conserved NPxxY(x)(5,6)F motif, through specific interactions with the receptor. The inferences are based on the analysis of microsecond length molecular dynamics (MD) simulations of rhodopsin in an explicit membrane environment. Three regions on the rhodopsin exhibit the highest cholesterol density throughout the trajectory: the extracellular end of TM7, a location resembling the high-density sterol area from the electron microscopy data; the intracellular parts of TM1, TM2, and TM4, a region suggested as the cholesterol binding site in the recent X-ray crystallography data on beta(2)-adrenergic GPCR; and the intracellular ends of TM2-TM3, a location that was categorized as the high cholesterol density area in multiple independent 100 ns MD simulations of the same system. We found that cholesterol primarily affects specific local perturbations of the helical TM domains such as the kinks in TM1, TM2, and TM7. These local distortions, in turn, relate to rigid-body motions of the TMs in the TM1-TM2-TM7-H8 bundle. The specificity of the effects stems from the nonuniform distribution of cholesterol around the protein. Through correlation analysis we connect local effects of cholesterol on structural perturbations with a regulatory role of cholesterol in the structural rearrangements involved in GPCR function.
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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.