Referenced in: none

Automatically associated channels: Kv10.1 , Kv12.1

Title: Structural, biochemical, and functional characterization of the cyclic nucleotide binding homology domain from the mouse EAG1 potassium channel.

Authors: Maria J Marques-Carvalho, Nirakar Sahoo, Frederick W Muskett, Ricardo S Vieira-Pires, Guillaume Gabant, Martine Cadene, Roland Schönherr, João H Morais-Cabral

Journal, date & volume: J. Mol. Biol., 2012 Oct 12 , 423, 34-46

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22732247

Abstract
KCNH channels are voltage-gated potassium channels with important physiological functions. In these channels, a C-terminal cytoplasmic region, known as the cyclic nucleotide binding homology (CNB-homology) domain displays strong sequence similarity to cyclic nucleotide binding (CNB) domains. However, the isolated domain does not bind cyclic nucleotides. Here, we report the X-ray structure of the CNB-homology domain from the mouse EAG1 channel. Through comparison with the recently determined structure of the CNB-homology domain from the zebrafish ELK (eag-like K(+)) channel and the CNB domains from the MlotiK1 and HCN (hyperpolarization-activated cyclic nucleotide-gated) potassium channels, we establish the structural features of CNB-homology domains that explain the low affinity for cyclic nucleotides. Our structure establishes that the "self-liganded" conformation, where two residues of the C-terminus of the domain are bound in an equivalent position to cyclic nucleotides in CNB domains, is a conserved feature of CNB-homology domains. Importantly, we provide biochemical evidence that suggests that there is also an unliganded conformation where the C-terminus of the domain peels away from its bound position. A functional characterization of this unliganded conformation reveals a role of the CNB-homology domain in channel gating.