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dc.contributor.authorAlaimo Campi, Alessandro ORCID
dc.contributor.authorAlberdi González, Araitz
dc.contributor.authorGomis Pérez, Carolina
dc.contributor.authorFernández Orth, Juncal
dc.contributor.authorBernardo Seisdedos, Ganeko
dc.contributor.authorMalo de la Fuente, Covadonga
dc.contributor.authorMillet Aguilar-Galindo, Oscar
dc.contributor.authorAreso Goiricelaya, María Pilar
dc.contributor.authorVillarroel Muñoz, Álvaro
dc.date.accessioned2016-02-26T10:07:07Z
dc.date.available2016-02-26T10:07:07Z
dc.date.issued2014-01-28
dc.identifier.citationPLOS ONE 9(1) : (2014) // Article ID e86711es
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/10810/17439
dc.description.abstractKv7.2 (KCNQ2) is the principal molecular component of the slow voltage gated M-channel, which strongly influences neuronal excitability. Calmodulin (CaM) binds to two intracellular C-terminal segments of Kv7.2 channels, helices A and B, and it is required for exit from the endoplasmic reticulum. However, the molecular mechanisms by which CaM controls channel trafficking are currently unknown. Here we used two complementary approaches to explore the molecular events underlying the association between CaM and Kv7.2 and their regulation by Ca2+. First, we performed a fluorometric assay using dansylated calmodulin (D-CaM) to characterize the interaction of its individual lobes to the Kv7.2 CaM binding site (Q2AB). Second, we explored the association of Q2AB with CaM by NMR spectroscopy, using N-15-labeled CaM as a reporter. The combined data highlight the interdependency of the N- and C-lobes of CaM in the interaction with Q2AB, suggesting that when CaM binds Ca2+ the binding interface pivots between the N-lobe whose interactions are dominated by helix B and the C-lobe where the predominant interaction is with helix A. In addition, Ca2+ makes CaM binding to Q2AB more difficult and, reciprocally, the channel weakens the association of CaM with Ca2+.es
dc.description.sponsorshipThis work was supported by grants from the Spanish Ministry of Education (BFU2012-39883 and BFU2009-07581), the Spanish Ion Channel Initiative Consolider project (CSD2008-00005), and the Basque Government (SAIOTEK SA-2006/00023 and 304211ENA9). A. Alaimo and C. Malo were partially funded by Fundacion Biofisica Bizkaia. J. Fernandez-Orth held a FPI fellowship from the Spanish Ministry of Science and Innovation (BES-2008-002314). A. Alberdi holds a JAE-predoctoral CSIC fellowship cofinanced with European Social Funds. G. Bernardo-Seisdedos holds a fellowship from the Basque Country Government (BFI-2011-159). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.es
dc.language.isoenges
dc.publisherPublic Library Sciencees
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.subjectpotassium channelses
dc.subjectcrystal-structurees
dc.subjectprotein-peptidees
dc.subjectsodium channeles
dc.subjectapo-calmodulines
dc.subjectgating-domaines
dc.subjectk+ channelses
dc.subjectiq motivees
dc.subjectbindinges
dc.subjectrecognitiones
dc.titlePivoting between Calmodulin Lobes Triggered by Calcium in the Kv7.2/Calmodulin Complexes
dc.typeinfo:eu-repo/semantics/articlees
dc.rights.holder2014 Alaimo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.es
dc.relation.publisherversionhttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0086711#abstract0es
dc.identifier.doi10.1371/journal.pone.0086711
dc.departamentoesFarmacologíaes_ES
dc.departamentoesBioquímica y biología moleculares_ES
dc.departamentoeuFarmakologiaes_ES
dc.departamentoeuBiokimika eta biologia molekularraes_ES
dc.subject.categoriaAGRICULTURAL AND BIOLOGICAL SCIENCES
dc.subject.categoriaMEDICINE
dc.subject.categoriaBIOCHEMISTRY AND MOLECULAR BIOLOGY


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