title: Structural insights into neuronal K+ channel-calmodulin complexes.
abstract: Calmodulin (CaM) is a ubiquitous intracellular calcium sensor that directly binds to and modulates a wide variety of ion channels. Despite the large repository of high-resolution structures of CaM bound to peptide fragments derived from ion channels, there is no structural information about CaM bound to a fully folded ion channel at the plasma membrane. To determine the location of CaM docked to a functioning KCNQ K(+) channel, we developed an intracellular tethered blocker approach to measure distances between CaM residues and the ion-conducting pathway. Combining these distance restraints with structural bioinformatics, we generated an archetypal quaternary structural model of an ion channel-CaM complex in the open state. These models place CaM close to the cytoplasmic gate, where it is well positioned to modulate channel function.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605-2324, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Mruk
authors.forename: Shiven M D
authors.initials: SM
authors.lastname: Shandilya
authors.forename: Robert O
authors.initials: RO
authors.lastname: Blaustein
authors.forename: Celia A
authors.initials: CA
authors.lastname: Schiffer
authors.forename: William R
authors.initials: WR
authors.lastname: Kobertz
mesh_terms: D000818:Animals; D001665:Binding Sites; D002147:Calmodulin / Q000737:chemistry*; D019295:Computational Biology / Q000379:methods; D003593:Cytoplasm / Q000378:metabolism; D007477:Ions; D051658:KCNQ2 Potassium Channel / Q000378:metabolism; D051659:KCNQ3 Potassium Channel / Q000378:metabolism; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D009474:Neurons / Q000378:metabolism*; D015221:Potassium Channels / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D019789:Tetraethylammonium / Q000737:chemistry; D014982:Xenopus laevis
chemical_list: D002147:Calmodulin; D007477:Ions; D051658:KCNQ2 Potassium Channel; D051659:KCNQ3 Potassium Channel; D015221:Potassium Channels; D019789:Tetraethylammonium