Key result
Mutations in the KAT1 voltage sensor revealed that Asp(95) assists S3-S4 membrane insertion, while Asp(105) and Arg(171) interact to prevent S4 release into the ER lumen.
Population
In vitro translation and translocation models of the hyperpolarization-activated potassium channel, KAT1
Comparison
Mutations in the S2, S3, and S4 segments vs Wild-type KAT1 or alternative mutations
Design
Preclinical
Authors
Loading...
No immediate clinical implications for channelopathies; leaves open relevance to native mammalian Kv channel biogenesis.
Specific charged residues in the S2, S3, and S4 segments of the KAT1 potassium channel are required for correct voltage sensor topology in the ER membrane through posttranslational electrostatic interactions.
Sato et al. (2003) studied this question. Mutations in S2, S3, and S4 segments (e.g., D95V, D105V, R171D) vs. Wild-type or other mutations was evaluated on Membrane topology of the voltage sensor in the ER membrane. Mutations in the KAT1 voltage sensor revealed that Asp(95) assists S3-S4 membrane insertion, while Asp(105) and Arg(171) interact to prevent S4 release into the ER lumen.
Synapse has enriched 3 closely related papers on similar clinical questions. Consider them for comparative context: