ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2002
Mutational analysis of the conserved cysteines of the rat P2X2 purinoceptor.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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Who cites it
49 citing papers in PubMed, 95 citations in OpenAlex.
- Article
- The P2X4 Receptor: Cellular and Molecular Characteristics of a Promising Neuroinflammatory Target.International journal of molecular sciences · 2022Review
- Neonatal Seizures and Purinergic Signalling.International journal of molecular sciences · 2020Review
- New Insights of the Zn(II)-Induced P2 × 4R Positive Allosteric Modulation: Role of Head Receptor Domain SS2/SS3, E160 and D170.International journal of molecular sciences · 2020Article
- Purinergic signalling in autoimmunity: A role for the P2X7R in systemic lupus erythematosus?Biomedical journal · 2016Review
- 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
- 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
- Conformational flexibility of the agonist binding jaw of the human P2X3 receptor is a prerequisite for channel opening.British journal of pharmacology · 2014Article
- Regulation of ATP-gated P2X channels: from redox signaling to interactions with other proteins.Antioxidants & redox signaling · 2014Review
- Potent and long-lasting inhibition of human P2X2 receptors by copper.Neuropharmacology · 2014Article
- Exploring the ATP-binding site of P2X receptors.Frontiers in cellular neuroscience · 2013Review
- Conserved extracellular cysteines differentially regulate the potentiation produced by Zn2+ in rat P2X4 receptors.European journal of pharmacology · 2013Article
- Molecular and functional properties of P2X receptors--recent progress and persisting challenges.Purinergic signalling · 2012Review
- Involvement of the cysteine-rich head domain in activation and desensitization of the P2X1 receptor.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- High potency zinc modulation of human P2X2 receptors and low potency zinc modulation of rat P2X2 receptors share a common molecular mechanism.The Journal of biological chemistry · 2012Article
- Conserved ectodomain cysteines are essential for rat P2X7 receptor trafficking.Purinergic signalling · 2012Article
- Molecular basis of selective antagonism of the P2X1 receptor for ATP by NF449 and suramin: contribution of basic amino acids in the cysteine-rich loop.British journal of pharmacology · 2012Article
- Differential roles of cysteine residues in the cellular trafficking, dimerization, and function of the high-density lipoprotein receptor, SR-BI.Biochemistry · 2011Article
- Activation and regulation of purinergic P2X receptor channels.Pharmacological reviews · 2011Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
P2X receptors are ATP-gated cation channels that are widely expressed in the brain. The extracellular domains of all seven P2X receptors contain 10 conserved cysteines, which could form disulfide bonds or binding sites for transition metals that modulate P2X receptors. To test whether these cysteines are critical for receptor function, we studied wild-type rat P2X(2) receptors and 10 mutant P2X(2) receptors, each containing an alanine substituted for a cysteine. Nine mutants were functional but had reduced maximum currents compared with wild-type P2X(2) expressed in either Xenopus oocytes or human embryonic kidney (HEK) 293 cells. The 10th mutant (C224A) did not respond to ATP when expressed in oocytes and gave very small currents in HEK 293 cells. Seven mutants (C113A, C124A, C130A, C147A, C158A, C164A, and C214A) showed rightward shifts (9- to 30-fold) in their ATP concentration-response relationships and very little potentiation by zinc. In contrast, C258A and C267A had EC(50) values similar to those of wild-type P2X(2) and were potentiated by zinc. Acidic pH potentiated wild-type and all mutant receptor currents. Despite the loss of zinc potentiation in seven mutants, these cysteines are unlikely to be exposed in the zinc-binding site, because [2-(trimethylammonium)ethyl] methanethiosulfonate bromide did not prevent zinc potentiation of wild-type receptor currents. On the basis of correlations in the maximum current, EC(50), zinc potentiation, and pH potentiation, we suggest that the following cysteine pairs form disulfide bonds: C113-C164, C214-C224, and C258-C267. We also suggest that C124, C130, C147, and C158 form two disulfide bonds, but we are unable to assign specific cysteine pairs to these two bonds.
Indexed as
Identifiers
12019306PMC6757666W2104253762What OpenQuestion holds
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.