Crystal structure of a voltage-gated K+ channel pore module in a closed state in lipid membranes

J Biol Chem. 2012 Dec 14;287(51):43063-70. doi: 10.1074/jbc.M112.415091. Epub 2012 Oct 24.

Abstract

Voltage-gated K(+) channels underlie the electrical excitability of cells. Each subunit of the functional tetramer consists of the tandem fusion of two modules, an N-terminal voltage-sensor and a C-terminal pore. To investigate how sensor coupling to the pore generates voltage-dependent channel opening, we solved the crystal structure and characterized the function of a voltage-gated K(+) channel pore in a lipid membrane. The structure of a functional channel in a membrane environment at 3.1 Å resolution establishes an unprecedented connection between channel structure and function. The structure is unique in delineating an ion-occupied ready to conduct selectivity filter, a confined aqueous cavity, and a closed activation gate, embodying a dynamic entity trapped in an unstable closed state.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Conserved Sequence
  • Crystallography, X-Ray
  • Ion Channel Gating
  • Lipid Bilayers / chemistry*
  • Listeria monocytogenes / metabolism*
  • Membrane Lipids / chemistry*
  • Models, Molecular
  • Molecular Sequence Data
  • Potassium Channels, Voltage-Gated / chemistry*
  • Protein Conformation

Substances

  • Lipid Bilayers
  • Membrane Lipids
  • Potassium Channels, Voltage-Gated