| First Author | Liang P | Year | 2009 |
| Journal | J Biol Chem | Volume | 284 |
| Issue | 8 | Pages | 4960-7 |
| PubMed ID | 19109250 | Mgi Jnum | J:147900 |
| Mgi Id | MGI:3842883 | Doi | 10.1074/jbc.M807704200 |
| Citation | Liang P, et al. (2009) Structural Insights into KChIP4a Modulation of Kv4.3 Inactivation. J Biol Chem 284(8):4960-7 |
| abstractText | 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. |
