ArticlePLoS computational biology2013
Lipid receptor S1P₁ activation scheme concluded from microsecond all-atom molecular dynamics simulations.
Article in PLoS computational biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 36 citations in OpenAlex.
- Article
- Structural basis for receptor selectivity and inverse agonism in S1PNature communications · 2022Article
- Helix 8 in chemotactic receptors of the complement system.PLoS computational biology · 2022Article
- Recent Advances in Structure, Function, and Pharmacology of Class A Lipid GPCRs: Opportunities and Challenges for Drug Discovery.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Computer simulations of protein-membrane systems.Progress in molecular biology and translational science · 2020Article
- Article
- Multiscale Simulations of Biological Membranes: The Challenge To Understand Biological Phenomena in a Living Substance.Chemical reviews · 2019Article
- 'Crystal' Clear? Lysophospholipid Receptor Structure Insights and Controversies.Trends in pharmacological sciences · 2018Review
- Exploring a new ligand binding site of G protein-coupled receptors.Chemical science · 2018Article
- Activation mechanisms of the first sphingosine-1-phosphate receptor.Protein science : a publication of the Protein Society · 2017Article
- Ligand chain length drives activation of lipid G protein-coupled receptors.Scientific reports · 2017Article
- Biological Effects of Naturally Occurring Sphingolipids, Uncommon Variants, and Their Analogs.Neuromolecular medicine · 2016Review
- Mechanistic Studies on the Stereoselectivity of the Serotonin 5-HT1A Receptor.Angewandte Chemie (International ed. in English) · 2016Article
- Lys39-Lysophosphatidate Carbonyl Oxygen Interaction Locks LPA1 N-terminal Cap to the Orthosteric Site and partners Arg124 During Receptor Activation.Scientific reports · 2015Article
- Quantifying conformational changes in GPCRs: glimpse of a common functional mechanism.BMC bioinformatics · 2015Article
- Sphingosine-1-phosphate metabolism: A structural perspective.Critical reviews in biochemistry and molecular biology · 2015Review
- Concerted dynamic motions of an FABP4 model and its ligands revealed by microsecond molecular dynamics simulations.Biochemistry · 2014Article
- Comparative molecular dynamics simulations of mitogen-activated protein kinase-activated protein kinase 5.International journal of molecular sciences · 2014Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sphingosine 1-phosphate (S1P) is a lysophospholipid mediator which activates G protein-coupled sphingosine 1-phosphate receptors and thus evokes a variety of cell and tissue responses including lymphocyte trafficking, endothelial development, integrity, and maturation. We performed five all-atom 700 ns molecular dynamics simulations of the sphingosine 1-phosphate receptor 1 (S1P₁) based on recently released crystal structure of that receptor with an antagonist. We found that the initial movements of amino acid residues occurred in the area of highly conserved W269⁶·⁴⁸ in TM6 which is close to the ligand binding location. Those residues located in the central part of the receptor and adjacent to kinks of TM helices comprise of a transmission switch. Side chains movements of those residues were coupled to the movements of water molecules inside the receptor which helped in the gradual opening of intracellular part of the receptor. The most stable parts of the protein were helices TM1 and TM2, while the largest movement was observed for TM7, possibly due to the short intracellular part starting with a helix kink at P⁷·⁵⁰, which might be the first helix to move at the intracellular side. We show for the first time the detailed view of the concerted action of the transmission switch and Trp (W⁶·⁴⁸) rotamer toggle switch leading to redirection of water molecules flow in the central part of the receptor. That event is a prerequisite for subsequent changes in intracellular part of the receptor involving water influx and opening of the receptor structure.
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