Hydrophobic Gating of Ion Permeation in Magnesium Channel CorA

PLoS Comput Biol. 2015 Jul 16;11(7):e1004303. doi: 10.1371/journal.pcbi.1004303. eCollection 2015 Jul.

Abstract

Ion channels catalyze ionic permeation across membranes via water-filled pores. To understand how changes in intracellular magnesium concentration regulate the influx of Mg2+ into cells, we examine early events in the relaxation of Mg2+ channel CorA toward its open state using massively-repeated molecular dynamics simulations conducted either with or without regulatory ions. The pore of CorA contains a 2-nm-long hydrophobic bottleneck which remained dehydrated in most simulations. However, rapid hydration or "wetting" events concurrent with small-amplitude fluctuations in pore diameter occurred spontaneously and reversibly. In the absence of regulatory ions, wetting transitions are more likely and include a wet state that is significantly more stable and more hydrated. The free energy profile for Mg2+ permeation presents a barrier whose magnitude is anticorrelated to pore diameter and the extent of hydrophobic hydration. These findings support an allosteric mechanism whereby wetting of a hydrophobic gate couples changes in intracellular magnesium concentration to the onset of ionic conduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cation Transport Proteins / chemistry*
  • Cation Transport Proteins / ultrastructure*
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / ultrastructure*
  • Hydrophobic and Hydrophilic Interactions
  • Ion Channel Gating
  • Ions / chemistry
  • Magnesium / chemistry*
  • Models, Chemical*
  • Molecular Dynamics Simulation*
  • Permeability
  • Water / chemistry*
  • Wettability

Substances

  • Cation Transport Proteins
  • CorA protein, E coli
  • Escherichia coli Proteins
  • Ions
  • Water
  • Magnesium