1B4I

Control of K+ Channel Gating by protein phosphorylation: structural switches of the inactivation gate, NMR, 22 structures

1B4I の概要

• エントリーDOI: 10.2210/pdb1b4i/pdb
• NMR情報: BMRB: 4477
• 分子名称: POTASSIUM CHANNEL (1 entity in total)
• 機能のキーワード: potassium channel, inactivation gate, phosphorylation, proton transport
• 由来する生物種: Homo sapiens
• 細胞内の位置: Membrane; Multi-pass membrane protein: Q03721
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3440.82

構造登録者

Antz, C.,Bauer, T.,Kalbacher, H.,Frank, R.,Covarrubias, M.,Kalbitzer, H.R.,Ruppersberg, J.P.,Baukrowitz, T.,Fakler, B. (登録日: 1998-12-22, 公開日: 1999-04-27, 最終更新日: 2024-10-23)

主引用文献

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

実験手法

SOLUTION NMR