ArticleThe Journal of biological chemistry2014
Ectodomain movements of an ATP-gated ion channel (P2X2 receptor) probed by disulfide locking.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 29 citations in OpenAlex.
- Mechanisms of ligand recognition and channel opening for P2X2 receptors in lipid nanodiscs.Science advances · 2026Article
- Mechanisms of ligand recognition and channel opening for P2X2 receptors in lipid nanodiscs.bioRxiv : the preprint server for biology · 2025Article
- Single-dose genome editing therapy rescues auditory and vestibular functions in adult mice with DFNA41 deafness.The Journal of clinical investigation · 2025Article
- P2X2 receptor subunit interfaces are missense variant hotspots, where mutations tend to increase apparent ATP affinity.British journal of pharmacology · 2022Article
- Generation and characterization of a P2rx2 V60L mouse model for DFNA41.Human molecular genetics · 2021Article
- Article
- Mapping a novel positive allosteric modulator binding site in the central vestibule region of human P2X7.Scientific reports · 2019Article
- Conformational changes during human P2X7 receptor activation examined by structural modelling and cysteine-based cross-linking studies.Purinergic signalling · 2017Article
- Purinergic control of lysenin's transport and voltage-gating properties.Purinergic signalling · 2016Article
- 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
- Key sites for P2X receptor function and multimerization: overview of mutagenesis studies on a structural basis.Current medicinal chemistry · 2015Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The ectodomain of the P2X receptor is formed mainly from two- or three-stranded β-sheets provided symmetrically by each of the three subunits. These enclose a central cavity that is closed off furthest from the plasma membrane (the turret) and that joins with the transmembrane helices to form the ion permeation pathway. Comparison of closed and open crystal structures indicates that ATP binds in a pocket positioned between strands provided by different subunits and that this flexes the β-sheets of the lower body and enlarges the central cavity: this pulls apart the outer ends of the transmembrane helices and thereby opens an aperture, or gate, where they intersect within the membrane bilayer. In the present work, we examined this opening model by introducing pairs of cysteines into the rat P2X2 receptor that might form disulfide bonds within or between subunits. Receptors were expressed in human embryonic kidney cells, and disulfide formation was assessed by observing the effect of dithiothreitol on currents evoked by ATP. Substitutions in the turret (P90C, P89C/S97C), body wall (S65C/S190C, S65C/D315C) and the transmembrane domains (V48C/I328C, V51C/I328C, S54C/I328C) strongly inhibited ATP-evoked currents prior to reduction with dithiothreitol. Western blotting showed that these channels also formed predominately as dimers and/or trimers rather than monomers. The results strongly support the channel opening mechanism proposed on the basis of available crystal structures.
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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.