1B4G

CONTROL OF K+ CHANNEL GATING BY PROTEIN PHOSPHORYLATION: STRUCTURAL SWITCHES OF THE INACTIVATION GATE, NMR, 22 STRUCTURES

Summary for 1B4G

• Entry DOI: 10.2210/pdb1b4g/pdb
• NMR Information: BMRB: 4476
• Descriptor: POTASSIUM CHANNEL (1 entity in total)
• Functional Keywords: potassium channel, inactivation gate, phosphorylation
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Multi-pass membrane protein: Q03721
• Total number of polymer chains: 1
• Total formula weight: 3360.84

Authors

Antz, C.,Bauer, T.,Kalbacher, H.,Frank, R.,Covarrubias, M.,Kalbitzer, H.R.,Ruppersberg, J.P.,Baukrowitz, T.,Fakler, B. (deposition date: 1998-12-22, release date: 1999-04-27, Last modification date: 2024-10-09)

Primary citation

Antz, C.,Bauer, T.,Kalbacher, H.,Frank, R.,Covarrubias, M.,Kalbitzer, H.R.,Ruppersberg, J.P.,Baukrowitz, T.,Fakler, B.
Control of K+ channel gating by protein phosphorylation: structural switches of the inactivation gate.
Nat.Struct.Biol., 6:146-150, 1999

PubMed Abstract: Fast N-type inactivation of voltage-dependent potassium (Kv) 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 Kv3.4 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.

PubMed: 10048926
DOI: 10.1038/5833

Experimental method

SOLUTION NMR