Probing the interaction between KCNE2 and KCNQ1 in their transmembrane regions.
KCNE1-KCNE5 are single membrane-spanning proteins that associate with voltage-gated potassium channels to diversify their function. Other than the KCNQ1/KCNE1 complex, little is known about how KCNE proteins work. We focus on KCNE2, which associates with KCNQ1 to form K channels critical for gastric acid secretion in parietal cells. We use cysteine (Cys)-scanning mutagenesis to probe the functional role of residues along the KCNE2 transmembrane domain (TMD) in modulating KCNQ1 function. There is an alpha-helical periodicity in how Cys substitutions along the KCNE2 TMD perturb KCNQ1 pore conductance/ion selectivity. However, positions where Cys substitutions perturb KCNQ1 gating kinetics cluster to the extracellular end and cytoplasmic half of the KCNE2 TMD. This is the first systematic perturbation analysis of a KCNE TMD. We propose that the KCNE2 TMD adopts an alpha-helical secondary structure with one face making intimate contact with the KCNQ1 pore domain, while the contacts with the KCNQ1 voltage-sensing domain appear more dynamic.
Department of Physiology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA.
Xian-Sheng
XS
Liu
Mei
M
Zhang
Min
M
Jiang
Dong-Mei
DM
Wu
Gea-Ny
GN
Tseng
D000595:Amino Acid Sequence; D000818:Animals; D002839:Chromans / Q000494:pharmacology; D003545:Cysteine / Q000502:physiology; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D051657:KCNQ1 Potassium Channel / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology; D014982:Xenopus laevis
D002839:Chromans; C420023:HMR 1556; C489619:KCNE2 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D024642:Potassium Channels, Voltage-Gated; D013449:Sulfonamides; D003545:Cysteine