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

Hydrophobic Gating of Ion Permeation in Magnesium Channel CorA.

Author information

1
Molecular Structure and Function, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.
2
Molecular Structure and Function, The Hospital for Sick Children, Toronto, Ontario, Canada.
3
Shared Hierarchical Academic Research Computing Network, Department of Physics and Astronomy, University of Waterloo, Waterloo, Ontario, Canada.
4
Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada; Ontario Cancer Institute/Princess Margaret Cancer Centre, Campbell Family Institute for Cancer Research, Toronto, Ontario, Canada.

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.

PMID:
26181442
PMCID:
PMC4504495
DOI:
10.1371/journal.pcbi.1004303
[Indexed for MEDLINE]
Free PMC Article

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