Hydrophobic Gating of Ion Permeation in Magnesium Channel CorA.
PLoS Comput Biol
; 11(7): e1004303, 2015 Jul.
Article
em En
| MEDLINE
| ID: mdl-26181442
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Água
/
Proteínas de Escherichia coli
/
Proteínas de Transporte de Cátions
/
Simulação de Dinâmica Molecular
/
Magnésio
/
Modelos Químicos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
PLoS Comput Biol
Assunto da revista:
BIOLOGIA
/
INFORMATICA MEDICA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Canadá