ArticleStructure (London, England : 1993)2019
Cholesterol Interaction Sites on the Transmembrane Domain of the Hedgehog Signal Transducer and Class F G Protein-Coupled Receptor Smoothened.
Article in Structure (London, England : 1993), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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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
54 citing papers in PubMed, 105 citations in OpenAlex.
- Atomic, structural and molecular insights into GPCR ligand binding and signalling.Nature reviews. Molecular cell biology · 2026Review
- Article
- Multiscale Simulation Approaches to Probe Lipid Interactions of G Protein-Coupled Receptors.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Oncogenic B-Raf proto-oncogene, serine/threonine kinase-mediated hedgehog signalling in the pathogenesis and targeted therapy of melanoma.World journal of clinical oncology · 2025Review
- Physics-based evolution of transmembrane helices reveals mechanisms of cholesterol attraction.Nature communications · 2025Article
- Membrane remodeling by the caveolin-1 8s oligomeric complex.Biophysical journal · 2025Article
- Effects of Membrane Cholesterol on the Structure and Function of Selected Class A GPCRs─Challenges and Future Perspectives.Biochemistry · 2025Review
- The Influence of Phosphoinositide Lipids in the Molecular Biology of Membrane Proteins: Recent Insights from Simulations.Journal of molecular biology · 2025Review
- The Role of Cholesterol in M2 Clustering and Viral Budding Explained.Journal of chemical theory and computation · 2025Article
- De novo variants in GABRA4 are associated with a neurological phenotype including developmental delay, behavioral abnormalities and epilepsy.European journal of human genetics : EJHG · 2024Article
- Improved Highly Mobile Membrane Mimetic Model for Investigating Protein-Cholesterol Interactions.Journal of chemical information and modeling · 2024Article
- Lipid regulation of the glucagon receptor family.The Journal of endocrinology · 2024Review
- Estimating the Cholesterol Affinity of Integral Membrane Proteins from Experimental Data.Biochemistry · 2024Article
- Fully activated structure of the sterol-bound Smoothened GPCR-Gi protein complex.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Cholesterol catalyzes unfolding in membrane-inserted motifs of the pore forming protein cytolysin A.Biophysical journal · 2023Article
- The energetics and ion coupling of cholesterol transport through Patched1.Science advances · 2023Article
- Dual mechanisms of cholesterol-GPCR interactions that depend on membrane phospholipid composition.Structure (London, England : 1993) · 2023Article
- Activation mechanism of the human Smoothened receptor.Biophysical journal · 2023Article
- Cholesterol in Class C GPCRs: Role, Relevance, and Localization.Membranes · 2023Article
- The Energetics and Ion Coupling of Cholesterol Transport Through Patched1.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Transduction of Hedgehog signals across the plasma membrane is facilitated by the class F G-protein-coupled-receptor (GPCR) Smoothened (SMO). Recent studies suggest that SMO is modulated via interactions of its transmembrane (TM) domain with cholesterol. We apply molecular dynamics simulations of SMO embedded in cholesterol containing lipid bilayers, revealing a direct interaction of cholesterol with the TM domain at regions distinct from those observed in class A GPCRs. In particular the extracellular tips of helices TM2 and TM3 form a well-defined cholesterol interaction site. Potential of mean force calculations yield a free energy landscape for cholesterol binding. Alongside analysis of equilibrium cholesterol occupancy, this reveals the existence of a dynamic "greasy patch" interaction with the TM domain of SMO, which may be compared with previously identified lipid interaction sites on other membrane proteins. These predictions provide molecular-level insights into cholesterol interactions with a class F GPCR, suggesting potential druggable 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.