NMR assignments of a 48 kDa tetramer of the T1 domain of the mammalian voltage gated potassium channel Kv1.4

Abstract

The N-terminal cytosolic T1 domain of the mammalian voltage gated potassium channel Kv1.4 is strongly involved in the tetramerization of the Kv1.4 subunit that is required for forming a functional ion channel. The T1 domain forms a stable tetramer of 48 kDa in solution that cannot be dissociated into monomers. In spite of the high molecular mass it was possible to completely assign the backbone and part of the side chain resonances by multidimensional NMR spectroscopy on uniformly (2)H, (13)C, (15)N enriched protein. The secondary structure analysis derived from the chemical shifts is in line with the expectations from X-ray structures of related proteins.

Discovery of a small molecule modulator of the Kv1.1/Kvβ1 channel complex that reduces neuronal excitability and in vitro epileptiform activity

“…This inactivation mechanism is mediated by the N‐terminal peptide of the Kvβ1 subunit that blocks the ion conduction pathway shortly after the channel has opened . The Kvβ1 protein is homologous to an aldoketoreductase that binds to a highly structured N‐terminal region of the Kv1.x channel (T1 domain) and the disruption of this protein complex, either by mutations or by small molecules, was shown to abolish the inactivation process …”