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 IKs 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 α-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.
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1 December 2006
Article|
November 27 2006
Secondary Structure of a KCNE Cytoplasmic Domain
Jessica M. Rocheleau,
Jessica M. Rocheleau
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605
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Steven D. Gage,
Steven D. Gage
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605
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William R. Kobertz
William R. Kobertz
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605
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Jessica M. Rocheleau
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605
Steven D. Gage
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605
William R. Kobertz
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605
Correspondence to William R. Kobertz: [email protected]
Abbreviations used in this paper: α-PI, α-periodicity index; E1–E5, KCNE1–KCNE5; HA, hemagglutinin A; Q1, KCNQ1; TEVC, two-electrode voltage clamp; WT, wild-type.
Received:
August 29 2006
Accepted:
October 27 2006
Online ISSN: 1540-7748
Print ISSN: 0022-1295
The Rockefeller University Press
2006
J Gen Physiol (2006) 128 (6): 721–729.
Article history
Received:
August 29 2006
Accepted:
October 27 2006
Citation
Jessica M. Rocheleau, Steven D. Gage, William R. Kobertz; Secondary Structure of a KCNE Cytoplasmic Domain . J Gen Physiol 1 December 2006; 128 (6): 721–729. doi: https://doi.org/10.1085/jgp.200609657
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