ArticleScientific reports2017
Ligand chain length drives activation of lipid G protein-coupled receptors.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 45 citations in OpenAlex.
- Structural mechanisms underlying distinct binding and activities of 18:0 and 18:1 lysophosphatidic acids at LPA1 receptor.PLoS computational biology · 2026Article
- Emerging complexities of phospholipid metabolism in adipose tissue.Molecules and cells · 2026Review
- Don't Be Surprised When These Surprise You: Some Infrequently Studied Sphingoid Bases, Metabolites, and Factors That Should Be Kept in Mind During Sphingolipidomic Studies.International journal of molecular sciences · 2025Review
- Atypical sphingosine-1-phosphate metabolites-biological implications of alkyl chain length.Pflugers Archiv : European journal of physiology · 2024Review
- The Leu/ValJournal of chemical information and modeling · 2023Article
- Structural insights into sphingosine-1-phosphate receptor activation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Differential activation mechanisms of lipid GPCRs by lysophosphatidic acid and sphingosine 1-phosphate.Nature communications · 2022Article
- Serine Palmitoyltransferase Subunit 3 and Metabolic Diseases.Advances in experimental medicine and biology · 2022Review
- Recent Advances in Structure, Function, and Pharmacology of Class A Lipid GPCRs: Opportunities and Challenges for Drug Discovery.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Mapping the Molecular Architecture Required for Lipid-Binding Pockets Using a Subset of Established and Orphan G-Protein Coupled Receptors.Journal of chemical information and modeling · 2021Article
- Endogenous agonist-bound S1PR3 structure reveals determinants of G protein-subtype bias.Science advances · 2021Article
- Preclinical and Clinical Evidence for the Involvement of Sphingosine 1-Phosphate Signaling in the Pathophysiology of Vascular Cognitive Impairment.Neuromolecular medicine · 2021Review
- Immunomodulatory sphingosine-1-phosphates as plasma biomarkers of Alzheimer's disease and vascular cognitive impairment.Alzheimer's research & therapy · 2020Article
- Positron Emission Tomography in the Inflamed Cerebellum: Addressing Novel Targets among G Protein-Coupled Receptors and Immune Receptors.Pharmaceutics · 2020Review
- A Novel Agonist of the Type 1 Lysophosphatidic Acid Receptor (LPAJournal of medicinal chemistry · 2020Article
- Activation of sphingosine 1-phosphate receptor 2 attenuates chemotherapy-induced neuropathy.The Journal of biological chemistry · 2020Article
- Article
- Experimental and computational analysis of biased agonism on full-length and a C-terminally truncated adenosine AComputational and structural biotechnology journal · 2020Article
- Characterization of Lipid-Protein Interactions and Lipid-Mediated Modulation of Membrane Protein Function through Molecular Simulation.Chemical reviews · 2019Review
- Changes in the Canine Plasma Lipidome after Short- and Long-Term Excess Glucocorticoid Exposure.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sphingosine-1-phosphate (S1P) is a lipid mediator that can activate five cell membrane G protein-coupled receptors (GPCRs) which carry a variety of essential functions and are promising drug targets. S1P is composed of a polar zwitterionic head-group and a hydrophobic alkyl chain. This implies an activation mechanism of its cognate receptor that must be significantly different from what is known for prototypical GPCRs (ie receptor to small hydrophilic ligands). Here we aim to identify the structural features responsible for S1P agonism by combining molecular dynamics simulations and functional assays using S1P analogs of different alkyl chain lengths. We propose that high affinity binding involves polar interactions between the lipid head-group and receptor side chains while activation is due to hydrophobic interactions between the lipid tail and residues in a distinct binding site. We observe that ligand efficacy is directly related to alkyl chain length but also varies with receptor subtypes in correlation with the size of this binding pocket. Integrating experimental and computational data, we propose an activation mechanism for the S1P receptors involving agonist-induced conformational events that are conserved throughout class A GPCRs.
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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.