Key result
The KCNE2 N-terminus decreased KCNQ1 surface expression and activity, while the transmembrane domains and C-termini of KCNE1 and KCNE2 interacted with KCNQ1 in different modes to modulate channel gating.
The study reveals that different regions of KCNE1 and KCNE2 auxiliary proteins modulate KCNQ1 channel function through distinct structural interaction modes and effects on surface expression.
Caution against extrapolating to human arrhythmias; extends mechanistic mapping of KCNE-KCNQ1 domains in animal models.
KCNQ1 channels play vital roles in cardiovascular, gastric and other systems. The conductance and dynamics of KCNQ1 could be modulated by different single transmembrane helical auxiliary proteins (such as KCNE1, KCNE2 and others). In this study, detail KCNQ1 function modulations by different regions of KCNE1 or KCNE2 were examined using combinational methods of electrophysiology, immunofluorescence, solution NMR and related backbone flexibility analysis. In the presence of KCNE2 N-terminus, decreased surface expression and consequent low activities of KCNQ1 were observed. The transmembrane domains (TMDs) of KCNE1 and KCNE2 were illustrated to associate with the KCNQ1 channel in different modes: Ile64 in KCNE2-TMD interacting with Phe340 and Phe275 in KCNQ1, while two pairs of interacting residues (Phe340-Thr58 and Ala244-Tyr65) in the KCNQ1/KCNE1 complex. The KCNE1 C-terminus could modulate gating property of KCNQ1, whereas KCNE2 C-terminus had only minimal influences on KCNQ1. All of the results demonstrated different KCNQ1 function modulations by different regions of the two auxiliary proteins.
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Li et al. (2014) studied KCNQ1 channel function. KCNE1 and KCNE2 chimeras and mutations vs. Wild-type KCNQ1 or KCNQ1/KCNE2 was evaluated on KCNQ1 channel conductance and surface expression. The KCNE2 N-terminus decreased KCNQ1 surface expression and activity, while the transmembrane domains and C-termini of KCNE1 and KCNE2 interacted with KCNQ1 in different modes to modulate channel gating.
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