Title: Structural insight into KCNQ (Kv7) channel assembly and channelopathy.

Authors: Rebecca J Howard, Kimberly A Clark, James M Holton, Daniel L Minor

Journal, date & volume: Neuron, 2007 Mar 1 , 53, 663-75

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/17329207

Abstract
Kv7.x (KCNQ) voltage-gated potassium channels form the cardiac and auditory I(Ks) current and the neuronal M-current. The five Kv7 subtypes have distinct assembly preferences encoded by a C-terminal cytoplasmic assembly domain, the A-domain Tail. Here, we present the high-resolution structure of the Kv7.4 A-domain Tail together with biochemical experiments that show that the domain is a self-assembling, parallel, four-stranded coiled coil. Structural analysis and biochemical studies indicate conservation of the coiled coil in all Kv7 subtypes and that a limited set of interactions encode assembly specificity determinants. Kv7 mutations have prominent roles in arrhythmias, deafness, and epilepsy. The structure together with biochemical data indicate that A-domain Tail arrhythmia mutations cluster on the solvent-accessible surface of the subunit interface at a likely site of action for modulatory proteins. Together, the data provide a framework for understanding Kv7 assembly specificity and the molecular basis of a distinct set of Kv7 channelopathies.