2018
Druggable negative allosteric site of P2X3 receptors
Wang J, Wang Y, Cui W, Huang Y, Yang Y, Liu Y, Zhao W, Cheng X, Sun W, Cao P, Zhu M, Wang R, Hattori M, Yu Y. Druggable negative allosteric site of P2X3 receptors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: 4939-4944. PMID: 29674445, PMCID: PMC5948998, DOI: 10.1073/pnas.1800907115.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric RegulationCrystallography, X-RayHEK293 CellsHumansModels, MolecularPhenyl EthersProtein DomainsPyrimidinesReceptors, Purinergic P2X3SulfonamidesConceptsAllosteric siteNegative allosteric siteDruggable allosteric sitesG protein-coupled receptorsAllosteric modulationLeft flipperProtein-coupled receptorsNew drug targetsDorsal fin domainLB domainsClinical trialsP2X receptorsAllosteric changesAllosteric inhibitorsChannel mutantsDrug targetsPhase II clinical trialFunctional studiesFin domainRefractory chronic coughIdiopathic pulmonary fibrosisIon channelsLower bodyX-ray crystallographyNegative allosteric modulation
2017
The nonproton ligand of acid-sensing ion channel 3 activates mollusk-specific FaNaC channels via a mechanism independent of the native FMRFamide peptide
Yang X, Niu Y, Liu Y, Yang Y, Wang J, Cheng X, Liang H, Wang H, Hu Y, Lu X, Zhu M, Xu T, Tian Y, Yu Y. The nonproton ligand of acid-sensing ion channel 3 activates mollusk-specific FaNaC channels via a mechanism independent of the native FMRFamide peptide. Journal Of Biological Chemistry 2017, 292: 21662-21675. PMID: 29123030, PMCID: PMC5766947, DOI: 10.1074/jbc.m117.814707.Peer-Reviewed Original ResearchConceptsDEG/ENaCDegenerin/epithelial sodium channelIon channelsAcid-sensing ion channelsMammalian acid-sensing ion channelsSodium channelsDiverse functionsKey residuesEpithelial sodium channelFMRFamide peptidesAncient featureChannel gatingActivation mechanismDistinct mechanismsSubfamiliesMammalsENaCUnitary conductancePathological processesNew insightsNonproton ligandIon selectivityEndogenous agonistSynaptic transmissionFaNaC