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Structural Insights into KChIP4a Modulation of Kv4.3 Inactivation
Ping Liang1, Huayi Wang, Hao Chen
1Department of Neurobiology, Neuroscience Research Institute, Key Laboratory for Neuroscience of the Ministry of Education, Center for Protein Sciences, Peking University, 38 Xueyuan Road, Beijing 100083, China.
The Journal of Biological Chemistry
|December 26, 2008
Summary
Structural differences in KChIP4a reveal how Kv channel-interacting proteins (KChIPs) modulate neuronal excitability. The KChIP4a N terminus acts as a slow inactivation gate for Kv4.3 channels.
Area of Science:
- Neuroscience
- Structural Biology
- Molecular Biology
Background:
- Dynamic inactivation of Kv4 A-type K(+) currents is crucial for neuronal excitability.
- KChIP1-4 subunits modulate Kv4 channel inactivation and surface expression differently.
- Structural basis for KChIP functional diversity was previously unknown.
Purpose of the Study:
- To determine the structural basis for KChIP functional diversity.
- To elucidate the mechanism by which KChIP4a regulates Kv4.3 channel inactivation.
Main Methods:
- X-ray crystallography of KChIP4a.
- Biochemical binding assays.
- Electrophysiology experiments.
Main Results:
- The crystal structure of KChIP4a revealed distinct N-terminal alpha-helices.
- Kv4.3 N-terminal peptide binding releases the KChIP4a N terminus, suppressing inactivation.
- KChIP4a N-terminal peptide confers slow inactivation to Kv4.3 channels.
Conclusions:
- KChIP4a's unique N-terminal structure differentiates it from other KChIPs.
- Kv4.3 binding to KChIP4a mobilizes the N terminus to act as a slow inactivation gate.
- This mechanism provides insight into the regulation of neuronal excitability.
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