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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

Team

Principal Investigator

Eduardo Perozo
Institution
University of Chicago

Team Members

Jamie Vandenberg
Institution
The Victor Chang Cardiac Research Institute

Carus Lau
Institution
The Victor Chang Cardiac Research Institute

Michael Clark
Institution
University of Chicago

Janette Myers
Institution
Oregon Health & Science University