ArticleProceedings of the National Academy of Sciences of the United States of America2012
Involvement of the cysteine-rich head domain in activation and desensitization of the P2X1 receptor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 68 citations in OpenAlex.
- Structural basis for a central permeation pathway in the P2X1 receptor.Cell discovery · 2026Article
- Species Differences of P2X4 Receptor Modulators.ACS pharmacology & translational science · 2025Article
- A shared mechanism for TNP-ATP recognition by members of the P2X receptor family.Computational and structural biotechnology journal · 2024Article
- Finely ordered intracellular domain harbors an allosteric site to modulate physiopathological function of P2X3 receptors.Nature communications · 2024Article
- Structural insights into the orthosteric inhibition of P2X receptors by non-ATP analog antagonists.eLife · 2024Article
- Article
- P2X2 receptor subunit interfaces are missense variant hotspots, where mutations tend to increase apparent ATP affinity.British journal of pharmacology · 2022Article
- Enlightening activation gating in P2X receptors.Purinergic signalling · 2022Review
- A 4/8 Subtype α-Conotoxin Vt1.27 Inhibits N-Type Calcium Channels With Potent Anti-Allodynic Effect.Frontiers in pharmacology · 2022Article
- Mapping the binding site of the P2X receptor antagonist PPADS reveals the importance of orthosteric site charge and the cysteine-rich head region.The Journal of biological chemistry · 2018Article
- Druggable negative allosteric site of P2X3 receptors.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Opposing Roles of Calcium and Intracellular ATP on Gating of the Purinergic P2X2 Receptor Channel.International journal of molecular sciences · 2018Article
- Structural insights into the competitive inhibition of the ATP-gated P2X receptor channel.Nature communications · 2017Article
- Intersubunit physical couplings fostered by the left flipper domain facilitate channel opening of P2X4 receptors.The Journal of biological chemistry · 2017Article
- The Dynamic Behavior of the P2XBiophysical journal · 2016Article
- Mechanistic insights from resolving ligand-dependent kinetics of conformational changes at ATP-gated P2X1R ion channels.Scientific reports · 2016Article
- The α2δ-1 subunit remodels CaV1.2 voltage sensors and allows Ca2+ influx at physiological membrane potentials.The Journal of general physiology · 2016Article
- Inter-subunit disulfide locking of the human P2X3 receptor elucidates ectodomain movements associated with channel gating.Purinergic signalling · 2016Article
- A Highly Conserved Salt Bridge Stabilizes the Kinked Conformation of β2,3-Sheet Essential for Channel Function of P2X4 Receptors.The Journal of biological chemistry · 2016Article
- Photo-switchable tweezers illuminate pore-opening motions of an ATP-gated P2X ion channel.eLife · 2016Article
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
P2X receptors (P2XRs) are ligand-gated ion channels activated by extracellular ATP. Although the crystal structure of the zebrafish P2X4R has been solved, the exact mode of ATP binding and the conformational changes governing channel opening and desensitization remain unknown. Here, we used voltage clamp fluorometry to investigate movements in the cysteine-rich head domain of the rat P2X1R (A118-I125) that projects over the proposed ATP binding site. On substitution with cysteine residues, six of these residues (N120-I125) were specifically labeled by tetramethyl-rhodamine-maleimide and showed significant changes in the emission of the fluorescence probe on application of the agonists ATP and benzoyl-benzoyl-ATP. Mutants N120C and G123C showed fast fluorescence decreases with similar kinetics as the current increases. In contrast, mutants P121C and I125C showed slow fluorescence increases that seemed to correlate with the current decline during desensitization. Mutant E122C showed a slow fluorescence increase and fast decrease with ATP and benzoyl-benzoyl-ATP, respectively. Application of the competitive antagonist 2',3'-O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP) resulted in large fluorescence changes with the N120C, E122C, and G123C mutants and minor or no changes with the other mutants. Likewise, TNP-ATP-induced changes in control mutants distant from the proposed ATP binding site were comparably small or absent. Combined with molecular modeling studies, our data confirm the proposed ATP binding site and provide evidence that ATP orients in its binding site with the ribose moiety facing the solution. We also conclude that P2XR activation and desensitization involve movements of the cysteine-rich head domain.
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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.