Closing in on the resting state of the Shaker K(+) channel

Neuron. 2007 Oct 4;56(1):124-40. doi: 10.1016/j.neuron.2007.09.023.


Membrane depolarization causes voltage-gated ion channels to transition from a resting/closed conformation to an activated/open conformation. We used voltage-clamp fluorometry to measure protein motion at specific regions of the Shaker Kv channel. This enabled us to construct new structural models of the resting/closed and activated/open states based on the Kv1.2 crystal structure using the Rosetta-Membrane method and molecular dynamics simulations. Our models account for the measured gating charge displacement and suggest a molecular mechanism of activation in which the primary voltage sensors, S4s, rotate by approximately 180 degrees as they move "outward" by 6-8 A. A subsequent tilting motion of the S4s and the pore domain helices, S5s, of all four subunits induces a concerted movement of the channel's S4-S5 linkers and S6 helices, allowing ion conduction. Our models are compatible with a wide body of data and resolve apparent contradictions that previously led to several distinct models of voltage sensing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Radiation
  • Electric Stimulation
  • Ion Channel Gating / physiology*
  • Membrane Potentials / physiology*
  • Membrane Potentials / radiation effects
  • Models, Biological
  • Models, Molecular
  • Mutation / physiology
  • Oocytes
  • Patch-Clamp Techniques / methods
  • Protein Conformation
  • Protein Structure, Tertiary
  • Shaker Superfamily of Potassium Channels / physiology*
  • Structure-Activity Relationship


  • Shaker Superfamily of Potassium Channels