Download MendeleyStructural Insights into KChIP4a Modulation of Kv4.3 Inactivation.
Liang, P., Wang, H., Chen, H., Cui, Y., Gu, L., Chai, J., Wang, K.(2009) J Biol Chem 284: 4960-4967
- PubMed: 19109250
- DOI: https://doi.org/10.1074/jbc.M807704200
- Primary Citation of Related Structures:
3DD4 - 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.
Organizational Affiliation:
Department 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.
