Structure of the inactivating gate from the Shaker voltage gated K+ channel analyzed by NMR spectroscopy

Rapid inactivation of voltage-gated K+ (K-v) channels is mediated by an N-terminal domain (inactivating ball domain) which blocks the open channel from the cytoplasmic side. Inactivating ball domains of various K-v channels are also biologically active when synthesized separately and added as a peptide to the solution. Synthetic inactivating ball domains from different K-v channels with hardly any sequence homology mediate quite similar effects even on unrelated K-v channel subtypes whose inactivation domain has been deleted. The solution structure of the inactivating ball peptide from Shaker (Sh-P22) was analyzed with NMR spectroscopy. The NMR data indicate a non-random structure in an aqueous environment. However, while other inactivating ball peptides showed well-defined three-dimensional structures under these conditions, Sh-P22 does not have a unique, compactly folded structure in solution.