3dd4
Structural Basis of KChIP4a Modulation of Kv4.3 Slow Inactivation
Structural highlights
FunctionKCIP4_MOUSE Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly inactivating A-type potassium channels. Probably modulates channels density, inactivation kinetics and rate of recovery from inactivation in a calcium-dependent and isoform-specific manner. In vitro, modulates KCND3/Kv4.3 and KCND2/Kv4.2 currents (By similarity).[1] [2] Publication Abstract from PubMedDynamic 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. Structural Insights into KChIP4a Modulation of Kv4.3 Inactivation.,Liang P, Wang H, Chen H, Cui Y, Gu L, Chai J, Wang K J Biol Chem. 2009 Feb 20;284(8):4960-7. Epub 2008 Dec 24. PMID:19109250[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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