NMR structure and functional characteristics of the hydrophilic N terminus of the potassium channel beta-subunit Kv beta 1.1

Wissmann, Ralph and Baukrowitz, Thomas and Kalbacher, Hubert and Kalbitzer, Hans Robert and Ruppersberg, Johannes Peter and Pongs, Olaf and Antz, Christoph and Fakler, Bernd (1999) NMR structure and functional characteristics of the hydrophilic N terminus of the potassium channel beta-subunit Kv beta 1.1. JOURNAL OF BIOLOGICAL CHEMISTRY, 274 (50). pp. 35521-35525. ISSN 0021-9258,

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Abstract

Rapid N-type inactivation of voltage-dependent potassium (Kv) channels controls membrane excitability and signal propagation in central neurons and is mediated by protein domains (inactivation gates) occluding the open channel pore from the cytoplasmic side, Inactivation domains (ID) are donated either by the pore-forming alpha-subunit or certain auxiliary beta-subunits. Upon coexpression, Kv beta 1.1 was found to endow non-inactivating members of the Kv1 alpha family with fast inactivation via its unique N terminus, Here we investigated structure and functional properties of the Kv beta 1.1 N terminus (amino acids 1-62, beta N-(1-62)) using NMR spectroscopy and patch clamp recordings, beta N-(1-62) showed all hallmarks of N-type inactivation: it inactivated non-inactivating Kv1.1 channels when applied to the cytoplasmic side as a synthetic peptide, and its interaction with the cu-subunit was competed with tetraethylammonium and displayed an affinity in the lower micromolar range. In aequous and physiological salt solution, beta N-(1-62) showed no well defined three-dimensional structure, it rather existed in a fast equilibrium of multiple weakly structured states. These structural and functional properties of beta N-(1-62) closely resemble those of the "unstructured" ID from Shaker B, but differ markedly from those of the compactly folded ID of the Kv3.4 alpha-subunit.

Item Type: Article
Uncontrolled Keywords: ACTIVATED K+ CHANNELS; BALL PEPTIDE; INACTIVATION; SPECTROSCOPY; ALPHA; MODULATION; BINDING; SPECTRA; PORE; GATE;
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: 06 Dec 2022 09:48
Last Modified: 06 Dec 2022 09:48
URI: https://pred.uni-regensburg.de/id/eprint/48769

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