ArticleProceedings of the National Academy of Sciences of the United States of America2016
Conductance of P2X4 purinergic receptor is determined by conformational equilibrium in the transmembrane region.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 24 citations in OpenAlex.
- Extended local deuteration of leucine enhances methyl NMR of large proteins expressed in eukaryotic cells.Chemical communications (Cambridge, England) · 2026Article
- A shared mechanism for TNP-ATP recognition by members of the P2X receptor family.Computational and structural biotechnology journal · 2024Article
- Function-Related Dynamics in Multi-Spanning Helical Membrane Proteins Revealed by Solution NMR.Membranes · 2021Review
- Local Deuteration Enables NMR Observation of Methyl Groups in Proteins from Eukaryotic and Cell-Free Expression Systems.Angewandte Chemie (International ed. in English) · 2021Article
- Sparse isotope labeling for nuclear magnetic resonance (NMR) of glycoproteins using 13C-glucose.Glycobiology · 2021Article
- Spotlight on the Ballet of Proteins: The Structural Dynamic Properties of Proteins Illuminated by Solution NMR.International journal of molecular sciences · 2020Review
- Conformational equilibrium defines the variable induction of the multidrug-binding transcriptional repressor QacR.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Function-related conformational dynamics of G protein-coupled receptors revealed by NMR.Biophysical reviews · 2019Review
- GPCR drug discovery: integrating solution NMR data with crystal and cryo-EM structures.Nature reviews. Drug discovery · 2019Review
- On the use of Pichia pastoris for isotopic labeling of human GPCRs for NMR studies.Journal of biomolecular NMR · 2018Review
- Deuteration and selective labeling of alanine methyl groups of βJournal of biomolecular NMR · 2018Article
- Structural basis for the ethanol action on G-protein-activated inwardly rectifying potassium channel 1 revealed by NMR spectroscopy.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Phosphorylation-induced conformation of βNature communications · 2018Article
- An Adaptable Phospholipid Membrane Mimetic System for Solution NMR Studies of Membrane Proteins.Journal of the American Chemical Society · 2017Article
- Structural insights into the competitive inhibition of the ATP-gated P2X receptor channel.Nature communications · 2017Article
- P2X4: A fast and sensitive purinergic receptor.Biomedical journal · 2017Review
- Intersubunit physical couplings fostered by the left flipper domain facilitate channel opening of P2X4 receptors.The Journal of biological chemistry · 2017Article
- Article
- Mechanistic insights from resolving ligand-dependent kinetics of conformational changes at ATP-gated P2X1R ion channels.Scientific reports · 2016Article
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ligand-gated ion channels are partially activated by their ligands, resulting in currents lower than the currents evoked by the physiological full agonists. In the case of P2X purinergic receptors, a cation-selective pore in the transmembrane region expands upon ATP binding to the extracellular ATP-binding site, and the currents evoked by α,β-methylene ATP are lower than the currents evoked by ATP. However, the mechanism underlying the partial activation of the P2X receptors is unknown although the crystal structures of zebrafish P2X4 receptor in the apo and ATP-bound states are available. Here, we observed the NMR signals from M339 and M351, which were introduced in the transmembrane region, and the endogenous alanine and methionine residues of the zebrafish P2X4 purinergic receptor in the apo, ATP-bound, and α,β-methylene ATP-bound states. Our NMR analyses revealed that, in the α,β-methylene ATP-bound state, M339, M351, and the residues that connect the ATP-binding site and the transmembrane region, M325 and A330, exist in conformational equilibrium between closed and open conformations, with slower exchange rates than the chemical shift difference (<100 s(-1)), suggesting that the small population of the open conformation causes the partial activation in this state. Our NMR analyses also revealed that the transmembrane region adopts the open conformation in the state bound to the inhibitor trinitrophenyl-ATP, and thus the antagonism is due to the closure of ion pathways, except for the pore in the transmembrane region: i.e., the lateral cation access in the extracellular region.
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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.