3DD4

Structural Basis of KChIP4a Modulation of Kv4.3 Slow Inactivation

3DD4 の概要

• エントリーDOI: 10.2210/pdb3dd4/pdb
• 分子名称: Kv channel-interacting protein 4, CALCIUM ION (3 entities in total)
• 機能のキーワード: ef-hands protein, ion transport, ionic channel, membrane, potassium, potassium channel, potassium transport, transport, voltage-gated channel, transport protein
• 由来する生物種: Mus musculus (mouse)
• 細胞内の位置: Cell membrane; Peripheral membrane protein: Q6PHZ8
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 26609.48

構造登録者

Chai, J.,Wang, H.,Wang, K. (登録日: 2008-06-05, 公開日: 2008-12-23, 最終更新日: 2023-11-01)

主引用文献

Liang, P.,Wang, H.,Chen, H.,Cui, Y.,Gu, L.,Chai, J.,Wang, K.
Structural Insights into KChIP4a Modulation of Kv4.3 Inactivation.
J.Biol.Chem., 284:4960-4967, 2009

PubMed 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.

PubMed: 19109250
DOI: 10.1074/jbc.M807704200

実験手法

X-RAY DIFFRACTION (3 Å)