Pivoting between Calmodulin Lobes Triggered by Calcium in the Kv7.2/Calmodulin Complex

• DOI: 10.1371/journal.pone.0086711
• Publication Date: 2014-01-28T21:33:33Z
• Authors: Alessandro Alaimo; Araitz Alberdi; Carolina Gomis-Perez; Juncal Fernández-...; Ganeko Bernardo-S...; Covadonga Malo; Oscar Millet; Pilar Areso; Alvaro Villarroel
• Keywords: Models, Molecular; 0301 basic medicine; binding; Magnetic Resonance Spectroscopy; BIOCHEMISTRY AND MOLECULAR BIOLOGY; Science; Molecular Sequence Data; Binding, Competitive; Protein Structure, Secondary; 03 medical and health sciences; Calmodulin; protein-peptide; iq motive; Animals; Humans; KCNQ2 Potassium Channel; Amino Acid Sequence; Ions; Binding Sites; apo-calmodulin; MEDICINE; Q; R; crystal-structure; potassium channels; Rats; k+ channels; Spectrometry, Fluorescence; gating-domain; AGRICULTURAL AND BIOLOGICAL SCIENCES; Medicine; Calcium; Mutant Proteins; recognition; sodium channel; Research Article; Protein Binding

Kv7.2 (KCNQ2) is the principal molecular component of slow voltage gated M-channel, which strongly influences neuronal excitability. Calmodulin (CaM) binds to two intracellular C-terminal segments channels, helices A and B, it required for exit from endoplasmic reticulum. However, mechanisms by CaM controls channel trafficking are currently unknown. Here we used complementary approaches explore events underlying association between their regulation Ca(2+). First, performed a fluorometric assay using dansylated calmodulin (D-CaM) characterize interaction its individual lobes binding site (Q2AB). Second, explored Q2AB with NMR spectroscopy, (15)N-labeled as reporter. The combined data highlight interdependency N- C-lobes in Q2AB, suggesting that when Ca(2+) interface pivots N-lobe whose interactions dominated helix B C-lobe where predominant A. In addition, makes more difficult and, reciprocally, weakens