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.

KCNH系列包含ERG，EAG和ELK电压激活的钾选择性通道。与其他K通道不同，KCNH通道包含独特的结构域，包括N端区域的PAS（Per-Arnt-Sim）域和C端区域的CNBHD（环状核苷酸结合同源域）。胞内PAS域和CNBHDs直接相互作用，并调节每种类型的KCNH通道的某些特征门控特性。PAS-CNBHD相互作用调节hERG通道的缓慢关闭（关闭），EAG通道中的激活动力学和依赖于脉冲前的闭合状态（Cole-Moore位移）的动力学以及ELK通道中的电压依赖性增强。KCNH通道均受与CNBHD结合的C端区域的固有配体基序调节。这里，