Hydrophobic Gating of Ion Permeation in Magnesium Channel CorA.
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 mol...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-07-01
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| Series: | PLoS Computational Biology |
| Online Access: | http://europepmc.org/articles/PMC4504495?pdf=render |
| Summary: | 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. |
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| ISSN: | 1553-734X 1553-7358 |