| Autor: |
Rocheleau JM; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA., Gage SD, Kobertz WR |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of general physiology [J Gen Physiol] 2006 Dec; Vol. 128 (6), pp. 721-9. |
| DOI: |
10.1085/jgp.200609657 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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