Recombinant Xenopus laevis Potassium voltage-gated channel subfamily KQT member 1 (kcnq1)
Description
Research Applications
Recombinant Xenopus KCNQ1 is widely used in electrophysiological and structural studies:
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Channel Trafficking and Regulation: Coexpression with KCNE1 in Xenopus oocytes reveals how accessory subunits modulate channel kinetics and membrane localization . For example, serum/glucocorticoid-regulated kinase 1 (SGK1) enhances KCNQ1/KCNE1 currents by promoting vesicular recycling to the plasma membrane .
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Structural Insights: Cryo-EM and NMR studies using recombinant KCNQ1 have resolved its voltage-sensing domain (VSD) in intermediate and activated states, critical for understanding conformational changes during gating .
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Drug Interactions: The protein serves as a template for screening compounds targeting cardiac arrhythmias or epithelial transport disorders .
Functional and Biophysical Findings
Key discoveries facilitated by recombinant Xenopus KCNQ1 include:
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Stoichiometric Flexibility: Coassembly with KCNE1 subunits occurs post-translationally, with variable ratios (4:2 to 4:4) influencing activation kinetics and current density .
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Voltage-Sensing Dynamics: The VSD adopts distinct intermediate (IO) and activated (AO) states, stabilized by interactions between residues E2-R4 and F0-Q3 .
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Pathogenic Mutations: Dominant-negative variants like G314S disrupt channel function by reducing current density, as shown in heterologous expression systems .
Comparative Analysis with Mammalian Homologs
While Xenopus KCNQ1 shares ~80% sequence identity with human KCNQ1, differences in regulatory domains affect drug binding and subunit interactions . For example:
Technical Considerations
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Reconstitution: Optimal activity requires reconstitution in liposomes or planar lipid bilayers, with glycerol (5–50%) enhancing stability .
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Limitations: The partial sequence lacks the C-terminal domain necessary for calmodulin binding, limiting studies on calcium-dependent regulation .
Future Directions
Current efforts focus on engineering full-length Xenopus KCNQ1 for cryo-EM studies and high-throughput drug screening . Integrating CRISPR-edited Xenopus models with recombinant protein assays will further clarify genotype-phenotype relationships in long QT syndrome .
Product Specs
Note: We will prioritize shipping the format currently in stock. However, if you have specific format requirements, please indicate them in your order notes. We will fulfill your request if possible.
Note: All our proteins are shipped with standard blue ice packs. If dry ice shipping is required, please inform us in advance, as additional fees will apply.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Target Background
- This study describes a physiological form of KCNQ1 characterized by depolarized voltage sensors with a closed pore in the absence of PIP2, and reveals a regulatory interaction between CaM and KCNQ1 that may explain CaM-mediated Long QT Syndrome. PMID: 28575668
- KCNE1/KCNQ1 was expressed in Xenopus oocytes both with and without beta-catenin. Confocal microscopy demonstrated that beta-catenin enhanced the abundance of KCNE1/KCNQ1 protein in the cell membrane. PMID: 22583083
- The findings indicate that AMPK inhibits KCNQ1 activity by promoting Nedd4-2-dependent channel ubiquitination and retrieval from the plasma membrane. PMID: 20861072
- S1 restricts S4 within the voltage sensor domain of Kv7.1 K+ channels. PMID: 18398461
- This research characterizes a novel component of the early bioelectrical circuit: the potassium channel KCNQ1 and its accessory subunit KCNE1. PMID: 18453744
- Slow delayed rectifier potassium currents mediated by mutant KCNQ1(Y111C) or KCNQ1(L114P) are paradoxically reduced by serum- and glucocorticoid-inducible kinase 1. PMID: 19008479
- Phenylboronic acid (PBA) activates KCNQ1/KCNE1 complexes. PMID: 19156197
KEGG: xla:373746
UniGene: Xl.21509
