ArticleThe Journal of biological chemistry2011
Cysteine scanning mutagenesis (residues Glu52-Gly96) of the human P2X1 receptor for ATP: mapping agonist binding and channel gating.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Article
- Role of Conserved Residues and F322 in the Extracellular Vestibule of the Rat P2X7 Receptor in Its Expression, Function and Dye Uptake Ability.International journal of molecular sciences · 2020Article
- 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
- Modeling Interactions among Individual P2 Receptors to Explain Complex Response Patterns over a Wide Range of ATP Concentrations.Frontiers in physiology · 2016Article
- Insights into the channel gating of P2X receptors from structures, dynamics and small molecules.Acta pharmacologica Sinica · 2016Review
- Glutathione release through connexin hemichannels: Implications for chemical modification of pores permeable to large molecules.The Journal of general physiology · 2015Article
- 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
- Ectodomain movements of an ATP-gated ion channel (P2X2 receptor) probed by disulfide locking.The Journal of biological chemistry · 2014Article
- Structural and molecular modeling features of P2X receptors.International journal of molecular sciences · 2014Review
- Principles and properties of ion flow in P2X receptors.Frontiers in cellular neuroscience · 2014Review
- Article
- Structural and functional properties of the rat P2X4 purinoreceptor extracellular vestibule during gating.Frontiers in cellular neuroscience · 2014Article
- Exploring the ATP-binding site of P2X receptors.Frontiers in cellular neuroscience · 2013Review
- Heteromeric assembly of P2X subunits.Frontiers in cellular neuroscience · 2013Review
- P2X receptor chimeras highlight roles of the amino terminus to partial agonist efficacy, the carboxyl terminus to recovery from desensitization, and independent regulation of channel transitions.The Journal of biological chemistry · 2013Article
- Spinal astrocytes produce and secrete dynorphin neuropeptides.Neuropeptides · 2013Article
- Multiple roles of the extracellular vestibule amino acid residues in the function of the rat P2X4 receptor.PloS one · 2013Article
- Article
- Mass spectrometry analysis of human P2X1 receptors; insight into phosphorylation, modelling and conformational changes.Journal of neurochemistry · 2012Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
P2X receptors are ATP-gated cation channels. The x-ray structure of a P2X4 receptor provided a major advance in understanding the molecular basis of receptor properties. However, how agonists are coordinated, the extent of the binding site, and the contribution of the vestibules in the extracellular domain to ionic permeation have not been addressed. We have used cysteine-scanning mutagenesis to determine the contribution of residues Glu(52)-Gly(96) to human P2X1 receptor properties. ATP potency was reduced for the mutants K68C, K70C, and F92C. The efficacy of the partial agonist BzATP was also reduced for several mutants forming the back of the proposed agonist binding site. Molecular docking in silico of both ATP and BzATP provided models of the agonist binding site consistent with these data. Individual cysteine mutants had no effect or slightly increased antagonism by suramin or pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate. Mutants at the entrance to and lining the upper vestibule were unaffected by cysteine-reactive methanethiosulfonate (MTS) reagents, suggesting that it does not contribute to ionic permeation. Mutants that were sensitive to modification by MTS reagents were predominantly found either around the proposed ATP binding pocket or on the strands connecting the binding pocket to the transmembrane region and lining the central vestibule. In particular, ATP sensitivity and currents were increased by a positively charged MTS reagent at the G60C mutant at the interface between the central and extracellular vestibule. This suggests that dilation of the base of the central vestibule contributes to gating of the receptor.
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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.