2021
An epilepsy-causing mutation leads to co-translational misfolding of the Kv7.2 channel
Urrutia J, Aguado A, Gomis-Perez C, Muguruza-Montero A, Ballesteros OR, Zhang J, Nuñez E, Malo C, Chung HJ, Leonardo A, Bergara A, Villarroel A. An epilepsy-causing mutation leads to co-translational misfolding of the Kv7.2 channel. BMC Biology 2021, 19: 109. PMID: 34020651, PMCID: PMC8138981, DOI: 10.1186/s12915-021-01040-1.Peer-Reviewed Original ResearchConceptsKv7.2 channelsChannel functionSequences of proteinsNon-native configurationsNascent chainsProper foldingEpilepsy-causing mutationsIQ motifResponsive domainHuman diseasesHelix ANative conformationFolding routeIon channelsKCNQ2 geneMutationsNeuronal compartmentsFoldingMisfoldingProteinKey pathogenic mechanismsPathogenic variantsSilico studiesPathogenic mechanismsSide chains
2018
Structural basis and energy landscape for the Ca2+ gating and calmodulation of the Kv7.2 K+ channel
Bernardo-Seisdedos G, Nuñez E, Gomis-Perez C, Malo C, Villarroel Á, Millet O. Structural basis and energy landscape for the Ca2+ gating and calmodulation of the Kv7.2 K+ channel. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: 2395-2400. PMID: 29463698, PMCID: PMC5873240, DOI: 10.1073/pnas.1800235115.Peer-Reviewed Original ResearchConceptsC-lobeKey biological signalsPrincipal molecular componentsAssociation of helicesTransmembrane regionStructural basisFunction of CaKv7.2 channelsBasal cytosolic CaConformational rearrangementsN-lobeInactive stateKey controllerMolecular componentsCytosolic CaIntracellular CaKv7.2HelixInactive channelsM-currentBiological signalsCalcification stateMillisecond timeNeuronal excitabilityPopulated excited statesLack of correlation between surface expression and currents in epileptogenic AB-calmodulin binding domain Kv7.2 potassium channel mutants
Alaimo A, Etxeberria A, Gómez-Posada JC, Gomis-Perez C, Fernández-Orth J, Malo C, Villarroel A. Lack of correlation between surface expression and currents in epileptogenic AB-calmodulin binding domain Kv7.2 potassium channel mutants. Channels 2018, 12: 299-310. PMID: 30126342, PMCID: PMC6161613, DOI: 10.1080/19336950.2018.1511512.Peer-Reviewed Original Research
2017
Calmodulin confers calcium sensitivity to the stability of the distal intracellular assembly domain of Kv7.2 channels
Alaimo A, Nuñez E, Aivar P, Fernández-Orth J, Gomis-Perez C, Bernardo-Seisdedos G, Malo C, Villarroel A. Calmodulin confers calcium sensitivity to the stability of the distal intracellular assembly domain of Kv7.2 channels. Scientific Reports 2017, 7: 13425. PMID: 29044210, PMCID: PMC5647379, DOI: 10.1038/s41598-017-13811-4.Peer-Reviewed Original Research
2015
Uncoupling PIP2-calmodulin regulation of Kv7.2 channels by an assembly destabilizing epileptogenic mutation
Alberdi A, Gomis-Perez C, Bernardo-Seisdedos G, Alaimo A, Malo C, Aldaregia J, Lopez-Robles C, Areso P, Butz E, Wahl-Schott C, Villarroel A. Uncoupling PIP2-calmodulin regulation of Kv7.2 channels by an assembly destabilizing epileptogenic mutation. Journal Of Cell Science 2015, 128: 4014-4023. PMID: 26359296, DOI: 10.1242/jcs.176420.Peer-Reviewed Original ResearchAn unconventional calmodulin-anchoring site within the AB module of Kv7.2 channels
Gomis-Perez C, Alaimo A, Fernandez-Orth J, Alberdi A, Aivar-Mateo P, Bernardo-Seisdedos G, Malo C, Areso P, Felipe A, Villarroel A. An unconventional calmodulin-anchoring site within the AB module of Kv7.2 channels. Journal Of Cell Science 2015, 128: 3155-3163. PMID: 26148514, DOI: 10.1242/jcs.174128.Peer-Reviewed Original Research
2014
The Ever Changing Moods of Calmodulin: How Structural Plasticity Entails Transductional Adaptability
Villarroel A, Taglialatela M, Bernardo-Seisdedos G, Alaimo A, Agirre J, Alberdi A, Gomis-Perez C, Soldovieri MV, Ambrosino P, Malo C, Areso P. The Ever Changing Moods of Calmodulin: How Structural Plasticity Entails Transductional Adaptability. Journal Of Molecular Biology 2014, 426: 2717-2735. PMID: 24857860, DOI: 10.1016/j.jmb.2014.05.016.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsC-lobeProtein Data Bank databaseStructure-function studiesDomain organizationProtein complexesCaM bindingHuman diseasesRole of CaMStructural plasticityGreat diversityCaM mutationsNew exciting avenuesThree-dimensional arrangementHuman pathophysiologyDiversity of targetsRemarkable varietyIndependent signalsCalmodulinDiversityExciting avenuesBindingRecent advancesTargetExceptional versatilityHelixPivoting between Calmodulin Lobes Triggered by Calcium in the Kv7.2/Calmodulin Complex
Alaimo A, Alberdi A, Gomis-Perez C, Fernández-Orth J, Bernardo-Seisdedos G, Malo C, Millet O, Areso P, Villarroel A. Pivoting between Calmodulin Lobes Triggered by Calcium in the Kv7.2/Calmodulin Complex. PLOS ONE 2014, 9: e86711. PMID: 24489773, PMCID: PMC3904923, DOI: 10.1371/journal.pone.0086711.Peer-Reviewed Original ResearchConceptsC-lobeC-terminal segmentPrincipal molecular componentsAssociation of CaMChannel traffickingKv7.2 channelsMolecular mechanismsMolecular eventsEndoplasmic reticulumN-lobeMolecular componentsHelix BCalmodulin complexHelix A.CalmodulinData highlightKv7.2Calmodulin lobesM channelsComplementary approachesNeuronal excitabilityFluorometric assayTraffickingReporterReticulum
2012
Cooperativity between calmodulin-binding sites in Kv7.2 channels
Alaimo A, Alberdi A, Gomis-Perez C, Fernández-Orth J, Gómez-Posada JC, Areso P, Villarroel A. Cooperativity between calmodulin-binding sites in Kv7.2 channels. Journal Of Cell Science 2012, 126: 244-253. PMID: 23203804, DOI: 10.1242/jcs.114082.Peer-Reviewed Original Research