Your browser doesn't support javascript.
loading
Mechanistic basis of the dynamic response of TWIK1 ionic selectivity to pH.
Chatelain, Franck C; Gilbert, Nicolas; Bichet, Delphine; Jauch, Annaïse; Feliciangeli, Sylvain; Lesage, Florian; Bignucolo, Olivier.
Afiliação
  • Chatelain FC; Université Côte d'Azur, Centre national de la recherche scientifique, Institut national de la santé et de la recherche médicale, Institut de pharmacologie moléculaire et cellulaire, 06560, Valbonne, France.
  • Gilbert N; Laboratories of Excellence, Ion Channel Science and Therapeutics, 06560, Valbonne, France.
  • Bichet D; Université Côte d'Azur, Centre national de la recherche scientifique, Institut national de la santé et de la recherche médicale, Institut de pharmacologie moléculaire et cellulaire, 06560, Valbonne, France.
  • Jauch A; Laboratories of Excellence, Ion Channel Science and Therapeutics, 06560, Valbonne, France.
  • Feliciangeli S; Université Côte d'Azur, Centre national de la recherche scientifique, Institut national de la santé et de la recherche médicale, Institut de pharmacologie moléculaire et cellulaire, 06560, Valbonne, France.
  • Lesage F; Laboratories of Excellence, Ion Channel Science and Therapeutics, 06560, Valbonne, France.
  • Bignucolo O; Immunodeficiency Laboratory, Department of Biomedicine, Basel, Switzerland.
Nat Commun ; 15(1): 3849, 2024 May 08.
Article em En | MEDLINE | ID: mdl-38719838
ABSTRACT
Highly selective for K+ at neutral pH, the TWIK1 channel becomes permeable to Na+ upon acidification. Using molecular dynamics simulations, we identify a network of residues involved in this unique property. Between the open and closed states previously observed by electron microscopy, molecular dynamics simulations show that the channel undergoes conformational changes between pH 7.5-6 involving residues His122, Glu235, Lys246 and Phe109. A complex network of interactions surrounding the selectivity filter at high pH transforms into a simple set of stronger interactions at low pH. In particular, His122 protonated by acidification moves away from Lys246 and engages in a salt bridge with Glu235. In addition, stacking interactions between Phe109 and His122, which stabilize the selectivity filter in its K+-selective state at high pH, disappear upon acidification. This leads to dissociation of the Phe109 aromatic side chain from this network, resulting in the Na+-permeable conformation of the channel.

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article