ArticleProceedings of the National Academy of Sciences of the United States of America2012
Agonist binding evokes extensive conformational changes in the extracellular domain of the ATP-gated human P2X1 receptor ion channel.
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 34 papers.
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Who cites it
34 citing papers in PubMed, 56 citations in OpenAlex.
- Nature-inspired solid-state proton diode membrane for high-performance force-electric conversion.Nature communications · 2026Article
- P2X2 receptor subunit interfaces are missense variant hotspots, where mutations tend to increase apparent ATP affinity.British journal of pharmacology · 2022Article
- Mapping a novel positive allosteric modulator binding site in the central vestibule region of human P2X7.Scientific reports · 2019Article
- 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
- Mapping the Allosteric Action of Antagonists A740003 and A438079 Reveals a Role for the Left Flipper in Ligand Sensitivity at P2X7 Receptors.Molecular pharmacology · 2018Article
- The ASIC3/P2X3 cognate receptor is a pain-relevant and ligand-gated cationic channel.Nature communications · 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
- Conformational changes during human P2X7 receptor activation examined by structural modelling and cysteine-based cross-linking studies.Purinergic signalling · 2017Article
- P2X4 ReceptorFrontiers in pharmacology · 2017Article
- P2X receptors.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2016Review
- Inter-subunit disulfide locking of the human P2X3 receptor elucidates ectodomain movements associated with channel gating.Purinergic signalling · 2016Article
- Photo-switchable tweezers illuminate pore-opening motions of an ATP-gated P2X ion channel.eLife · 2016Article
- Insights into the channel gating of P2X receptors from structures, dynamics and small molecules.Acta pharmacologica Sinica · 2016Review
- Roles of the lateral fenestration residues of the P2X₄ receptor that contribute to the channel function and the deactivation effect of ivermectin.Purinergic signalling · 2015Article
- The use of SMALPs as a novel membrane protein scaffold for structure study by negative stain electron microscopy.Biochimica et biophysica acta · 2015Article
- Use of chimeras, point mutants, and molecular modeling to map the antagonist-binding site of 4,4',4″,4‴-(carbonylbis-(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakisbenzene-1,3-disulfonic acid (NF449) at P2X1 receptors for ATP.The Journal of biological chemistry · 2015Article
- Key sites for P2X receptor function and multimerization: overview of mutagenesis studies on a structural basis.Current medicinal chemistry · 2015Review
- Voltage- and ATP-dependent structural rearrangements of the P2X2 receptor associated with the gating of the pore.The Journal of physiology · 2014Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
P2X receptors for ATP have a wide range of physiological roles and comprise a structurally distinct family of ligand-gated trimeric ion channels. The crystal structure of a P2X4 receptor, in combination with mutagenesis studies, has provided a model of the intersubunit ATP-binding sites and identified an extracellular lateral portal, adjacent to the membrane, that funnels ions to the channel pore. However, little is known about the extent of ATP-induced conformational changes in the extracellular domain of the receptor. To address this issue, we have used MTSEA-biotinylation (N-Biotinoylaminoethyl methanethiosulfonate) to show ATP-sensitive accessibility of cysteine mutants at the human P2X1 receptor. Mapping these data to a P2X1 receptor homology model identifies significant conformational rearrangement. Electron microscopy of purified P2X1 receptors showed marked changes in structure on ATP binding, and introducing disulphide bonds between adjacent subunits to restrict intersubunit movements inhibited channel function. These results are consistent with agonist-induced rotation of the propeller-head domain of the receptor, sliding of adjacent subunits leading to restricted access to the upper vestibule, movement in the ion conducting lateral portals, and gating of the channel pore.
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Registered trials
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.