STRUCTURE OF THE INACTIVATING GATE FROM THE SHAKER VOLTAGE-GATED K-SPECTROSCOPY( CHANNEL ANALYZED BY NMR)

Rapid inactivation of voltage-gated K+ (K-v) channels is mediated by a n N-terminal domain (inactivating ball domain) which blocks the open c hannel 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 d omains from different K-v channels with hardly any sequence homology m ediate quite similar effects even on unrelated K-v channel subtypes wh ose inactivation domain has been deleted. The solution structure of th e inactivating ball peptide from Shaker (Sh-P22) was analyzed with NMR spectroscopy. The NMR data indicate a non-random structure in an aque ous environment. However, while other inactivating ball peptides showe d well-defined three-dimensional structures under these conditions, Sh -P22 does not have a unique, compactly folded structure in solution.