Pivoting between calmodulin lobes triggered by calcium in the Kv7.2/calmodulin complex.

Kv7.2 (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. How...

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Autores principales:	Alessandro Alaimo, Araitz Alberdi, Carolina Gomis-Perez, Juncal Fernández-Orth, Ganeko Bernardo-Seisdedos, Covadonga Malo, Oscar Millet, Pilar Areso, Alvaro Villarroel
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dca1fc06521041f5b0972c7720bcbb4a
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spelling	oai:doaj.org-article:dca1fc06521041f5b0972c7720bcbb4a2021-11-18T08:35:22ZPivoting between calmodulin lobes triggered by calcium in the Kv7.2/calmodulin complex.1932-620310.1371/journal.pone.0086711https://doaj.org/article/dca1fc06521041f5b0972c7720bcbb4a2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24489773/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Kv7.2 (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 Ca(2+). 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 (15)N-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 Ca(2+) 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, Ca(2+) makes CaM binding to Q2AB more difficult and, reciprocally, the channel weakens the association of CaM with Ca(2+).Alessandro AlaimoAraitz AlberdiCarolina Gomis-PerezJuncal Fernández-OrthGaneko Bernardo-SeisdedosCovadonga MaloOscar MilletPilar AresoAlvaro VillarroelPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e86711 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alessandro Alaimo Araitz Alberdi Carolina Gomis-Perez Juncal Fernández-Orth Ganeko Bernardo-Seisdedos Covadonga Malo Oscar Millet Pilar Areso Alvaro Villarroel Pivoting between calmodulin lobes triggered by calcium in the Kv7.2/calmodulin complex.
description	Kv7.2 (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 Ca(2+). 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 (15)N-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 Ca(2+) 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, Ca(2+) makes CaM binding to Q2AB more difficult and, reciprocally, the channel weakens the association of CaM with Ca(2+).
format	article
author	Alessandro Alaimo Araitz Alberdi Carolina Gomis-Perez Juncal Fernández-Orth Ganeko Bernardo-Seisdedos Covadonga Malo Oscar Millet Pilar Areso Alvaro Villarroel
author_facet	Alessandro Alaimo Araitz Alberdi Carolina Gomis-Perez Juncal Fernández-Orth Ganeko Bernardo-Seisdedos Covadonga Malo Oscar Millet Pilar Areso Alvaro Villarroel
author_sort	Alessandro Alaimo
title	Pivoting between calmodulin lobes triggered by calcium in the Kv7.2/calmodulin complex.
title_short	Pivoting between calmodulin lobes triggered by calcium in the Kv7.2/calmodulin complex.
title_full	Pivoting between calmodulin lobes triggered by calcium in the Kv7.2/calmodulin complex.
title_fullStr	Pivoting between calmodulin lobes triggered by calcium in the Kv7.2/calmodulin complex.
title_full_unstemmed	Pivoting between calmodulin lobes triggered by calcium in the Kv7.2/calmodulin complex.
title_sort	pivoting between calmodulin lobes triggered by calcium in the kv7.2/calmodulin complex.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/dca1fc06521041f5b0972c7720bcbb4a
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Pivoting between calmodulin lobes triggered by calcium in the Kv7.2/calmodulin complex.

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