ArticleScience advances2021
Endogenous agonist-bound S1PR3 structure reveals determinants of G protein-subtype bias.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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The trial behind it
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
26 citing papers in PubMed, 49 citations in OpenAlex.
- Potential Role of Sphingosine-1-Phosphate and Its Receptors in the Reparative Processes of the Adult Brain.International journal of molecular sciences · 2026Review
- Structural insights into subtype-specific agonist recognition by sphingosine-1-phosphate receptors.PLoS biology · 2026Article
- Molecular insights into ligand recognition and signaling of OXGR1.Nature communications · 2025Article
- Structural insights into the G-protein subtype selectivity revealed by human sphingosine-1-phosphate receptor 3-GProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Membrane disruption attenuates agonist potency in prostanoid receptors.The Biochemical journal · 2025Article
- The Genetics of Acne.Annals of human genetics · 2025Review
- Regulation of CXCR4 function by S1PCell communication and signaling : CCS · 2025Article
- Structural mechanisms of potent lysophosphatidic acid receptor 1 activation by nonlipid basic agonists.Communications biology · 2024Article
- Regulation of cellular and systemic sphingolipid homeostasis.Nature reviews. Molecular cell biology · 2024Review
- G Protein-Coupled Receptor-Ligand Pose and Functional Class Prediction.International journal of molecular sciences · 2024Article
- Structural basis for ligand recognition and signaling of the lysophosphatidylserine receptors GPR34 and GPR174.PLoS biology · 2023Article
- Structural basis of antibody inhibition and chemokine activation of the human CC chemokine receptor 8.Nature communications · 2023Article
- S1P-S1PR3-RAS promotes the progression of S1PR3Leukemia · 2023Article
- The Leu/ValJournal of chemical information and modeling · 2023Article
- Molecular and neuroimmune pharmacology of S1P receptor modulators and other disease-modifying therapies for multiple sclerosis.Pharmacology & therapeutics · 2023Review
- Sphingosine-1-Phosphate Signaling in Cardiovascular Diseases.Biomolecules · 2023Review
- Inhibiting a promiscuous GPCR: iterative discovery of bitter taste receptor ligands.Cellular and molecular life sciences : CMLS · 2023Article
- Biased signaling due to oligomerization of the G protein-coupled platelet-activating factor receptor.Nature communications · 2022Article
- Structure of the active GNature communications · 2022Article
- Structural basis for receptor selectivity and inverse agonism in S1PNature communications · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sphingosine-1-phosphate (S1P) regulates numerous important physiological functions, including immune response and vascular integrity, via its cognate receptors (S1PR1 to S1PR5); however, it remains unclear how S1P activates S1PRs upon binding. Here, we determined the crystal structure of the active human S1PR3 in complex with its natural agonist S1P at 3.2-Å resolution. S1P exhibits an unbent conformation in the long tunnel, which penetrates through the receptor obliquely. Compared with the inactive S1PR1 structure, four residues surrounding the alkyl tail of S1P (the "quartet core") exhibit orchestrating rotamer changes that accommodate the moiety, thereby inducing an active conformation. In addition, we reveal that the quartet core determines G protein selectivity of S1PR3. These results offer insight into the structural basis of activation and biased signaling in G protein-coupled receptors and will help the design of biased ligands for optimized therapeutics.
Identifiers
What Socratic holds
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 Socratic graph.