ArticleThe EMBO journal1998
P2X1 and P2X3 receptors form stable trimers: a novel structural motif of ligand-gated ion channels.
Article in The EMBO journal, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 197 papers.
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Who cites it
197 citing papers in PubMed, 554 citations in OpenAlex.
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- Discovery of an allosteric binding site for anthraquinones at the human P2X4 receptor.Nature communications · 2025Article
- Bayesian inference of functional asymmetry in the homotrimeric ligand-gated ion channel P2XCommunications biology · 2025Article
- Structural basis of the multiple ligand binding mechanisms of the P2X1 receptor.Acta pharmacologica Sinica · 2025Article
- The Multifaceted Role of P2X7R in Microglia and Astrocytes.Neurochemical research · 2025Review
- Article
- Cell Type-Specific Expression of Purinergic P2X Receptors in the Hypothalamus.International journal of molecular sciences · 2025Review
- Two serial filters control P2X7 cation selectivity, Ser342 in the central pore and lateral acidic residues at the cytoplasmic interface.PNAS nexus · 2024Article
- Expanding the genetic and phenotypic relevance of CLCN4 variants in neurodevelopmental condition: 13 new patients.Journal of neurology · 2024Article
- Increased Purinergic Signaling in Human Dental Pulps With Inflammatory Pain is Sex-Dependent.The journal of pain · 2024Article
- Purinergic Signaling and its Role in the Stem Cell Differentiation.Mini reviews in medicinal chemistry · 2024Review
- Migraine signaling pathways: purine metabolites that regulate migraine and predispose migraineurs to headache.Molecular and cellular biochemistry · 2023Review
- Alterations of Purinergic Receptors Levels and Their Involvement in the Glial Cell Morphology in a Pre-Clinical Model of Autism Spectrum Disorders.Brain sciences · 2023Article
- Purinergic signaling: Diverse effects and therapeutic potential in cancer.Frontiers in oncology · 2023Review
- Resensitization of TRPV1 channels after the P2 receptor activation in sensory neurons of spinal ganglia in rats.Frontiers in cellular neuroscience · 2023Article
- Diclofenac and other non-steroidal anti-inflammatory drugs (NSAIDs) are competitive antagonists of the human P2X3 receptor.Frontiers in pharmacology · 2023Article
- Alternatively Spliced Isoforms of the P2X7 Receptor: Structure, Function and Disease Associations.International journal of molecular sciences · 2022Review
- Enlightening activation gating in P2X receptors.Purinergic signalling · 2022Review
- Functional Characterization ofFrontiers in molecular neuroscience · 2022Article
- Glycosides for Peripheral Neuropathic Pain: A Potential Medicinal Components.Molecules (Basel, Switzerland) · 2021Review
137 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledP2X receptors are cation channels gated by extracellular ATP. The seven known P2X isoforms possess no sequence homology with other proteins. Here we studied the quaternary structure of P2X receptors by chemical cross-linking and blue native PAGE. P2X1 and P2X3 were N-terminally tagged with six histidine residues to allow for non-denaturing receptor isolation from cRNA-injected, [35S]methionine-labeled oocytes. The His-tag did not change the electrophysiological properties of the P2X1 receptor. His-P2X1 was found to carry four N-glycans per polypeptide chain, only one of which acquired Endo H resistance en route to the plasma membrane. 3, 3'-Dithiobis(sulfosuccinimidylpropionate) (DTSSP) and two of three bifunctional analogues of the P2X receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) cross-linked digitonin-solubilized His-P2X1 and His-P2X3 quantitatively to homo-trimers. Likewise, when analyzed by blue native PAGE, P2X receptors purified in digitonin or dodecyl-beta-D-maltoside migrated entirely as non-covalently linked homo-trimers, whereas the alpha2 beta gamma delta nicotinic acetylcholine receptor (used as a positive control) migrated as the expected pentamer. P2X monomers remained undetected soon after synthesis, indicating that trimerization occurred in the endoplasmic reticulum. The plasma membrane form of His-P2X1 was also identified as a homo-trimer. If n-octylglucoside was used for P2X receptor solubilization, homo-hexamers were observed, suggesting that trimers can aggregate to form larger complexes. We conclude that trimers represent an essential element of P2X receptor structure. KEYWORDS: blue native PAGE/cross-linking/P2X receptor/quaternary structure.
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