Antz, Christoph and Bauer, Tanja and Kalbacher, Hubert and Frank, Rainer and Covarrubias, Manuel and Kalbitzer, Hans Robert and Ruppersberg, Johannes Peter and Baukrowitz, Thomas and Fakler, Bernd (1999) Control of K+ channel gating by protein phosphorylation: structural switches of the inactivation gate. NATURE STRUCTURAL BIOLOGY, 6 (2). pp. 146-150. ISSN 1072-8368,
Full text not available from this repository. (Request a copy)Abstract
Fast N-type inactivation of voltage-dependent potassium (K-v) channels controls membrane excitability and signal propagation in central neurons and occurs by a 'ball-and-chain'-type mechanism, In this mechanism an N-terminal protein domain (inactivation gate) occludes the pore from the cytoplasmic side. In K(v)3.4 channels, inactivation is not fixed but is dynamically regulated by protein phosphorylation, Phosphorylation of several identified serine residues on the inactivation gate leads to reduction or removal of fast inactivation. Here, we investigate the structure-function basis of this phospho-regulation with nuclear magnetic resonance (NMR) spectroscopy and patch-clamp recordings using synthetic inactivation domains (ID), The dephosphorylated ID exhibited compact structure and displayed high-affinity binding to its receptor. Phosphorylation of serine residues in the N- or C-terminal half of the ID resulted in a loss of overall structural stability. However, depending on the residue(s) phosphorylated, distinct structural elements remained stable, These structural changes correlate with the distinct changes in binding and unbinding kinetics underlying the reduced inactivation potency of phosphorylated IDs.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | POTASSIUM CHANNELS; NMR-SPECTROSCOPY; KINASE; PROPAGATION; SPECTRA; NEURONS; PEPTIDE; BRAIN; SITE; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Dr. Hans Robert Kalbitzer |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Nov 2022 13:43 |
| Last Modified: | 22 Nov 2022 13:43 |
| URI: | https://pred.uni-regensburg.de/id/eprint/48562 |
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