Referenced in: none

Automatically associated channels: KChIP1 , Kv1.4 , Kv3.1 , Kv4.3 , Slo1

Title: Structural Insights into KChIP4a Modulation of Kv4.3 Inactivation.

Authors: Ping Liang, Huayi Wang, Hao Chen, Yuanyuan Cui, Lichuan Gu, Jijie Chai, Kewei Wang

Journal, date & volume: J. Biol. Chem., 2009 Feb 20 , 284, 4960-7

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19109250

Abstract
Dynamic inactivation in Kv4 A-type K(+) current plays a critical role in regulating neuronal excitability by shaping action potential waveform and duration. Multifunctional auxiliary KChIP1-4 subunits, which share a high homology in their C-terminal core regions, exhibit distinctive modulation of inactivation and surface expression of pore-forming Kv4 subunits. However, the structural differences that underlie the functional diversity of Kv channel-interacting proteins (KChIPs) remain undetermined. Here we have described the crystal structure of KChIP4a at 3.0A resolution, which shows distinct N-terminal alpha-helices that differentiate it from other KChIPs. Biochemical experiments showed that competitive binding of the Kv4.3 N-terminal peptide to the hydrophobic groove of the core of KChIP4a causes the release of the KChIP4a N terminus that suppresses the inactivation of Kv4.3 channels. Electrophysiology experiments confirmed that the first N-terminal alpha-helix peptide (residues 1-34) of KChIP4a, either by itself or fused to N-terminal truncated Kv4.3, can confer slow inactivation. We propose that N-terminal binding of Kv4.3 to the core of KChIP4a mobilizes the KChIP4a N terminus, which serves as the slow inactivation gate.