title: Regulatory interaction of sodium channel IQ-motif with calmodulin C-terminal lobe.
abstract: An increasing number of ion channels have been found to be regulated by the direct binding of calmodulin (CaM), but its structural features are mostly unknown. Previously, we identified the Ca(2+)-dependent and -independent interactions of CaM to the voltage-gated sodium channel via an IQ-motif sequence. In this study we used the trypsin-digested CaM fragments (TR(1)C and TR(2)C) to analyze the binding of Ca(2+)-CaM or Ca(2+)-free (apo) CaM with a sodium channel-derived IQ-motif peptide (NaIQ). Circular dichroic spectra showed that NaIQ peptide enhanced alpha-helicity of the CaM C-terminal lobe, but not that of the CaM N-terminal lobe in the absence of Ca(2+), whereas NaIQ enhanced the alpha-helicity of both the N- and C-terminal lobes in the presence of Ca(2+). Furthermore, the competitive binding experiment demonstrated that Ca(2+)-dependent CaM binding of target peptides (MLCKp or melittin) with CaM was markedly suppressed by NaIQ. The results suggest that IQ-motif sequences contribute to prevent target proteins from activation at low Ca(2+) concentrations and may explain a regulatory mechanism why highly Ca(2+)-sensitive target proteins are not activated in the cytoplasm.
authors.affiliation: Department of Information Physiology, National Institute for Physiological Sciences, Okazaki, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Mori
authors.forename: Takashi
authors.initials: T
authors.lastname: Konno
authors.forename: Takashi
authors.initials: T
authors.lastname: Morii
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Nagayama
authors.forename: Keiji
authors.initials: K
authors.lastname: Imoto
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002147:Calmodulin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D002942:Circular Dichroism; D008555:Melitten / Q000737:chemistry / Q000378:metabolism; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D015222:Sodium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D002147:Calmodulin; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D010455:Peptides; D015222:Sodium Channels; C065738:MLCK peptide; D008555:Melitten