Gating and regulation of KCNH (ERG, EAG, and ELK) channels by intracellular domains
Abstract
The KCNH family comprises the ERG, EAG, and ELK voltage-activated, potassium-selective channels. Distinct from other K channels, KCNH channels contain unique structural domains, including a PAS (Per-Arnt-Sim) domain in the N-terminal region and a CNBHD (cyclic nucleotide-binding homology domain) in the C-terminal region. The intracellular PAS domains and CNBHDs interact directly and regulate some of the characteristic gating properties of each type of KCNH channel. The PAS-CNBHD interaction regulates slow closing (deactivation) of hERG channels, the kinetics of activation and pre-pulse dependent population of closed states (the Cole-Moore shift) in EAG channels and voltage-dependent potentiation in ELK channels. KCNH channels are all regulated by an intrinsic ligand motif in the C-terminal region which binds to the CNBHD. Here, we focus on some recent advances regarding the PAS-CNBHD interaction and the intrinsic ligand.Keyword
CNBHD cyclic nucleotide-binding domainEAG K channel
ELK K channel
LQTS
PAS domain
hERG
intrinsic ligand
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http://hdl.handle.net/10713/13747ae974a485f413a2113503eed53cd6c53
10.1080/19336950.2020.1816107
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