A Leucine Zipper Motif Essential for Gating of Hyperpolarization-activated Channels.
In: Journal of Biological Chemistry, Jg. 287 (2012-11-23), Heft 48, S. 40150-40160
academicJournal
Zugriff:
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are pacemakers in cardiac myocytes and neurons. Although their membrane topology closely resembles that of voltage-gated K+ channels, the mechanism of their unique gating behavior in response to hyperpolarization is still poorly understood. We have identified a highly conserved leucine zipper motif in the S5 segment of HCN family members. In order to study the role of this motif for channel function, the leucine residues of the zipper were individually mutated to alanine, arginine, or glutamine residues. Leucine zipper mutants traffic to the plasma membrane, but the channels lose their sensitivity to open upon hyperpolarization. Thus, our data indicate that the leucine zipper is an important molecular determinant for hyperpolarization- activated channel gating. Residues of the leucine zipper interact with the adjacent S6 segment of the channel. This interaction is essential for voltage-dependent gating of the channel. The lower part of the leucine zipper, at the intracellular mouth of the channel, is important for stabilizing the closed state. Mutations at these sites increase current amplitudes or result in channels with deficient closing and increased min-Po. Our data are further supported by homology models of the open and closed state of the HCN2 channel pore. Thus, we conclude that the leucine zipper of HCN channels is a major determinant for hyperpolarization-activated channel gating. [ABSTRACT FROM AUTHOR]
Titel: |
A Leucine Zipper Motif Essential for Gating of Hyperpolarization-activated Channels.
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Autor/in / Beteiligte Person: | Wemhöner, Konstantin ; Silbernagel, Nicole ; Marzian, Stefanie ; Netter, Michael F. ; Rinné, Susanne ; Stansfeld, Phillip J. ; Decher, Niels |
Zeitschrift: | Journal of Biological Chemistry, Jg. 287 (2012-11-23), Heft 48, S. 40150-40160 |
Veröffentlichung: | 2012 |
Medientyp: | academicJournal |
ISSN: | 0021-9258 (print) |
DOI: | 10.1074/jbc.M112.378513 |
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