1B4I: Control of K+ Channel Gating by protein phosphorylation: structural switches of the inactivation gate, NMR, 22 structures

Citation:
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.
PDB ID: 1B4IDownload
MMDB ID: 55435
PDB Deposition Date: 1998/12/22
Updated in MMDB: 2007/10
Experimental Method:
solution nmr
Source Organism:
Similar Structures:
Molecular Components in 1B4I
Label Count Molecule
Protein (1 molecule)
1
Potassium Channel(Gene symbol: KCNC4)
Molecule annotation
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