Artículo
Positively charged residues in the head domain of P2X4 receptors assist the binding of ATP
Racigh, Vanesa Elizabeth
; Ormazábal, Agustín
; Palma, Juliana Isabel
; Pierdominici Sottile, Gustavo
Fecha de publicación:
11/2019
Editorial:
American Chemical Society
Revista:
Journal of Chemical Information and Modeling
ISSN:
1549-9596
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
P2X receptors are a family of trimeric cationic channels located in the membrane of mammalian cells. They open in response to the binding of ATP. The differences between the closed and open structures have been described in detail for some members of the family. However, the order in which the conformational changes take place as ATP enters the binding cleft, and the residues involved in the intermediate stages, are still unknown. Here, we present the results of umbrella sampling simulations aimed to elucidate the sequence of conformational changes that occur during the reversible binding of ATP to the P2X4 receptor. The simulations also provided information about the interactions that develop in the course of the process. In particular, they revealed the existence of a metastable state which assists the binding. This state is stabilized by positively charged residues located in the head domain of the receptor. Based on these findings, we propose a novel mechanism for the capture of ATP by P2X4 receptors.
Palabras clave:
Molecular Dynamics
,
P2X Receptors
,
Umbrella Sampling
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Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Articulos de SEDE CENTRAL
Citación
Racigh, Vanesa Elizabeth; Ormazábal, Agustín; Palma, Juliana Isabel; Pierdominici Sottile, Gustavo; Positively charged residues in the head domain of P2X4 receptors assist the binding of ATP; American Chemical Society; Journal of Chemical Information and Modeling; 60; 2; 11-2019; 923-932
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