title: Secondary structure of a KCNE cytoplasmic domain.
abstract: Type I transmembrane KCNE peptides contain a conserved C-terminal cytoplasmic domain that abuts the transmembrane segment. In KCNE1, this region is required for modulation of KCNQ1 K(+) channels to afford the slowly activating cardiac I(Ks) current. We utilized alanine/leucine scanning to determine whether this region possesses any secondary structure and to identify the KCNE1 residues that face the KCNQ1 channel complex. Helical periodicity analysis of the mutation-induced perturbations in voltage activation and deactivation kinetics of KCNQ1-KCNE1 complexes defined that the KCNE1 C terminus is alpha-helical when split in half at a conserved proline residue. This helical rendering assigns all known long QT mutations in the KCNE1 C-terminal domain as protein facing. The identification of a secondary structure within the KCNE1 C-terminal domain provides a structural scaffold to map protein-protein interactions with the pore-forming KCNQ1 subunit as well as the cytoplasmic regulatory proteins anchored to KCNQ1-KCNE complexes.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Rocheleau
authors.forename: Steven D
authors.initials: SD
authors.lastname: Gage
authors.forename: William R
authors.initials: WR
authors.lastname: Kobertz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003593:Cytoplasm / Q000737:chemistry; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000737:chemistry*; D016297:Mutagenesis, Site-Directed; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D014982:Xenopus laevis
chemical_list: C489622:KCNE1 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D024642:Potassium Channels, Voltage-Gated