Referenced in: none

Automatically associated channels: Kv7.2 , Slo1

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

Authors: Alessandro Alaimo, Araitz Alberdi, Carolina Gomis-Perez, Juncal Fernández-Orth, Ganeko Bernardo-Seisdedos, Covadonga Malo, Oscar Millet, Pilar Areso, Alvaro Villarroel

Journal, date & volume: PLoS ONE, 2014 , 9, e86711

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24489773

Abstract
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+).