ArticleThe Journal of biological chemistry2010
Conserved water-mediated hydrogen bond network between TM-I, -II, -VI, and -VII in 7TM receptor activation.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 56 citations in OpenAlex.
- Evaluation of a melanocortin-4 receptor (MC4R) agonist (Setmelanotide) in MC4R deficiency.Molecular metabolism · 2017Trial
- Visualize Transient Water-Mediated Hydrogen Bonds Facilitating the Formation of Enzymatic Near-Attack Conformers.JACS Au · 2025Article
- Computational design of highly signalling-active membrane receptors through solvent-mediated allosteric networks.Nature chemistry · 2025Article
- Structural insights into angiotensin receptor signaling modulation by balanced and biased agonists.The EMBO journal · 2023Article
- Mechanistic basis of GPCR activation explored by ensemble refinement of crystallographic structures.Protein science : a publication of the Protein Society · 2022Article
- Enhanced Thermostability of D-Psicose 3-Epimerase fromInternational journal of molecular sciences · 2021Article
- Novel Sequence Feature of SecA Translocase Protein Unique to the Thermophilic Bacteria: Bioinformatics Analyses to Investigate Their Potential Roles.Microorganisms · 2019Article
- Calcium-sensing receptor residues with loss- and gain-of-function mutations are located in regions of conformational change and cause signalling bias.Human molecular genetics · 2018Article
- Evolutionary action and structural basis of the allosteric switch controlling βNature communications · 2017Article
- Enhancing Structure Prediction and Design of Soluble and Membrane Proteins with Explicit Solvent-Protein Interactions.Structure (London, England : 1993) · 2017Article
- Evolution of nonspectral rhodopsin function at high altitudes.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- G Protein-Coupled Receptors Contain Two Conserved Packing Clusters.Biophysical journal · 2017Article
- Agonist Binding to Chemosensory Receptors: A Systematic Bioinformatics Analysis.Frontiers in molecular biosciences · 2017Article
- Chlorophyll-Derivative Modulation of Rhodopsin Signaling Properties through Evolutionarily Conserved Interaction Pathways.Frontiers in molecular biosciences · 2017Article
- Vibrational resonance, allostery, and activation in rhodopsin-like G protein-coupled receptors.Scientific reports · 2016Article
- Structure-Activity Analysis of Biased Agonism at the Human Adenosine A3 Receptor.Molecular pharmacology · 2016Article
- Can Specific Protein-Lipid Interactions Stabilize an Active State of the Beta 2 Adrenergic Receptor?Biophysical journal · 2015Article
- Biased Gs versus Gq proteins and β-arrestin signaling in the NK1 receptor determined by interactions in the water hydrogen bond network.The Journal of biological chemistry · 2015Article
- Quantifying conformational changes in GPCRs: glimpse of a common functional mechanism.BMC bioinformatics · 2015Article
- Retinal ligand mobility explains internal hydration and reconciles active rhodopsin structures.Biochemistry · 2014Article
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Five highly conserved polar residues connected by a number of structural water molecules together with two rotamer micro-switches, TrpVI:13 and TyrVII:20, constitute an extended hydrogen bond network between the intracellular segments of TM-I, -II, -VI, and -VII of 7TM receptors. Molecular dynamics simulations showed that, although the fewer water molecules in rhodopsin were relatively movable, the hydrogen bond network of the beta2-adrenergic receptor was fully loaded with water molecules that were surprisingly immobilized between the two rotamer switches, both apparently being in their closed conformation. Manipulations of the rotamer state of TyrVII:20 and TrpVI:13 demonstrated that these residues served as gates for the water molecules at the intracellular and extracellular ends of the hydrogen bond network, respectively. TrpVI:13 at the bottom of the main ligand-binding pocket was shown to apparently function as a catching trap for water molecules. Mutational analysis of the beta2-adrenergic receptor demonstrated that the highly conserved polar residues of the hydrogen bond network were all important for receptor signaling but served different functions, some dampening constitutive activity (AsnI:18, AspII:10, and AsnVII:13), whereas others (AsnVII:12 and AsnVII:16) located one helical turn apart and sharing a water molecule were shown to be essential for agonist-induced signaling. It is concluded that the conserved water hydrogen bond network of 7TM receptors constitutes an extended allosteric interface between the transmembrane segments being of crucial importance for receptor signaling and that part of the function of the rotamer micro-switches, TyrVII:20 and TrpVI:13, is to gate or trap the water molecules.
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