Open AccessPore conformations and gating mechanism of a Cys-loop receptor
Author(s) -
Yoav Paas,
Gilad Gibor,
Régis Grailhe,
Nathalie Savatier-Duclert,
Virginie Dufresne,
Morten Sunesen,
Lia Prado de Carvalho,
JeanPierre Changeux,
Bernard Attali
Publication year - 2005
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0507599102
Subject(s) - gating , biophysics , ion channel , chemistry , intracellular , crystallography , chemical physics , receptor , biochemistry , biology
Neurons regulate the propagation of chemoelectric signals throughout the nervous system by opening and closing ion channels, a process known as gating. Here, histidine-based metal-binding sites were engineered along the intrinsic pore of a chimeric Cys-loop receptor to probe state-dependent Zn(2+)-channel interactions. Patterns of Zn(2+) ion binding within the pore reveal that, in the closed state, the five pore-lining segments adopt an oblique orientation relative to the axis of ion conduction and constrict into a physical gate at their intracellular end. The interactions of Zn(2+) with the open state indicate that the five pore-lining segments should rigidly tilt to enable the movement of their intracellular ends away from the axis of ion conduction, so as to open the constriction (i.e., the gate). Alignment of the functional results with the 3D structure of an acetylcholine receptor allowed us to generate structural models accounting for the closed and open pore conformations and for a gating mechanism of a Cys-loop receptor.