Helmholtz Gemeinschaft


A carboxy-terminal domain determines the subunit specificity of KCNQ K+ channel assembly

Item Type:Article
Title:A carboxy-terminal domain determines the subunit specificity of KCNQ K+ channel assembly
Creators Name:Schwake, M., Jentsch, T.J. and Friedrich, T.
Abstract:Mutations in KCNQ K(+) channel genes underlie several human pathologies. KCNQ alpha-subunits form either homotetramers or hetero-oligomers with a restricted subset of other KCNQ alpha-subunits or with KCNE beta-subunits. KCNQ1 assembles with KCNE beta-subunits but not with other KCNQ alpha-subunits. By contrast, KCNQ3 interacts with KCNQ2, KCNQ4 and KCNQ5. Using a chimaeric strategy, we show that a cytoplasmic carboxy-terminal subunit interaction domain (sid) suffices to transfer assembly properties between KCNQ3 and KCNQ1. A chimaera (KCNQ1-sid(Q3)) carrying the si domain of KCNQ3 within the KCNQ1 backbone interacted with KCNQ2, KCNQ3 and KCNQ4 but not with KCNQ1. This interaction was shown by enhancement of KCNQ2 currents, testing for dominant-negative effects of pore mutants, determining its effects on surface expression and co-immunoprecipitation experiments. Conversely, a KCNQ3-sid(Q1) chimaera no longer affects KCNQ2 but interacts with KCNQ1. We conclude that the si domain suffices to determine the subunit specificity of KCNQ channel assembly.
Keywords:Amino Acid Sequence, Complementary DNA, KCNQ Potassium Channels, Macromolecular Substances, Molecular Sequence Data, Oocytes, Voltage-Gated Potassium Channels, Protein Binding, Protein Interaction Mapping, Tertiary Protein Structure, Recombinant Fusion Proteins, Sequence Alignment, Structure-Activity Relationship, Animals, Xenopus Laevis
Source:EMBO Reports
Publisher:Nature Publishing Group
Page Range:76-81
Date:January 2003
Official Publication:https://doi.org/10.1038/sj.embor.embor715
PubMed:View item in PubMed

Repository Staff Only: item control page

Open Access
MDC Library