biostudies-literatureXu QAmerican Heart AssociationNIDCD NIH HHSNHLBI NIH HHSNational Institutes of Health378-94https://www.ebi.ac.uk/biostudies/studies/S-EPMC3540129biostudies-literatureUnknown425(2)Calmodulin (CaM) is an important regulator of Kv7.x (KCNQx) voltage-gated potassium channels. Channels from this family produce neuronal M currents and cardiac and auditory I(KS) currents and harbor mutations that cause arrhythmias, epilepsy, and deafness. Despite extensive functional characterization, biochemical and structural details of the interaction between CaM and the channel have remained elusive. Here, we show that both apo-CaM and Ca(2+)/CaM bind to the C-terminal tail of the neuronal channel Kv7.4 (KCNQ4), which is involved in both hearing and mechanosensation. Interactions between apo-CaM and the Kv7.4 tail involve two C-terminal tail segments, known as the A and B segments, whereas the interaction between Ca(2+)/CaM and the Kv7.4 C-terminal tail requires only the B segment. BiJournal of molecular biologyStructure of a Ca(2+)/CaM:Kv7.4 (KCNQ4) B-helix complex provides insight into M current modulation.PMC3540129R01 DC007664T32 HL0077310740019NTolia AChang AXu QMinor DLfalseStructure of a Ca(2+)/CaM:Kv7.4 (KCNQ4) B-helix complex provides insight into M current modulation.Calmodulin (CaM) is an important regulator of Kv7.x (KCNQx) voltage-gated potassium channels. Channels from this family produce neuronal M currents and cardiac and auditory I(KS) currents and harbor mutations that cause arrhythmias, epilepsy, and deafness. Despite extensive functional characterization, biochemical and structural details of the interaction between CaM and the channel have remained elusive. Here, we show that both apo-CaM and Ca(2+)/CaM bind to the C-terminal tail of the neuronal channel Kv7.4 (KCNQ4), which is involved in both hearing and mechanosensation. Interactions between apo-CaM and the Kv7.4 tail involve two C-terminal tail segments, known as the A and B segments, whereas the interaction between Ca(2+)/CaM and the Kv7.4 C-terminal tail requires only the B segment. Bi2013-01-01T00:00:00Z2013 Jan2026-04-15T21:08:45.616Z2026-04-07T14:01:34.086ZS-EPMC35401292317817010.1016/j.jmb.2012.11.023