Products/Services Used | Details | Operation |
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Plasmid DNA Preparation | The QuikChange site-directed mutagenesis kit (Agilent, Santa Clara, CA, USA) was used to create all mutations except K449A. Kv3.1a-K449A and the corresponding WT without the FLAG tag were generated synthetically in the pcDNA3.1(+) vector (GenScript, Piscataway, NJ). | Get A Quote |
Kv3 channels have distinctive gating kinetics tailored for rapid repolarization in fast-spiking neurons. Malfunction of this process due to genetic variants in the KCNC1 gene causes severe epileptic disorders, yet the structural determinants for the unusual gating properties remain elusive. Here, we present cryo-electron microscopy structures of the human Kv3.1a channel, revealing a unique arrangement of the cytoplasmic tetramerization domain T1 which facilitates interactions with C-terminal axonal targeting motif and key components of the gating machinery. Additional interactions between S1/S2 linker and turret domain strengthen the interface between voltage sensor and pore domain. Supported by molecular dynam... More