Structural Basis of Voltage-Gating in Eukaryotic Potassium Channels
EMSL Project ID
50997
Abstract
Voltage-gated potassium (Kv) channels determine the resting membrane potential in eukaryotic cells, and thus control cellular excitability, cell volume and cell division. Aberrant potassium channel function leads to diseases ranging from epilepsy to cancer, yet the fundamental activation mechanisms of Kv channels are poorly understood. We recently determined the closed-state structure of a novel Kv channel by single particle cryo-EM. Based on this structure, we have designed several mutations to stabilize open and intermediate states of this Kv channel. We propose to determine the structure of at least one of these mutants in order to elucidate the conformational changes that occur upon Kv channel activation. If successful, our structure determination will provide a framework for interpretation of decades of functional data, as well as inform future mechanism-based therapeutics targeting Kv channels.
Project Details
Start Date
2019-08-01
End Date
2020-01-14
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members