A Salt Bridge Links CNBhD Conformation to the Gating Machinery in EAG Potassium Channels

Abstract

EAG, ERG and ELK are members of the Ether-à-go-go voltage-gated potassium channel family (1). Each channel possesses a C-terminal domain that is homologous to the cyclic nucleotide-binding domain of CNG/HCN channels but insensitive to cyclic nucleotides (2,3). X-ray crystallography of EAG suggests that the binding pocket of this region, termed the cyclic nucleotide-binding homology domain (CNBhD), is intrinsically “liganded” by the side chains of two residues, Y699 and L701 (4,8). To test this hypothesis, Y699 and L701 were substituted with alanines (AA) to mimic an “unliganded” state.