Pore conformations and gating mechanism of a Cys-loop receptor

Yoav Paas, Gilad Gibor, Regis Grailhe, Nathalie Savatier-Duclert, Virginie Dufresne, Morten Sunesen, Lia Prado De Carvalho, Jean Pierre Changeux, Bernard Attali

Research output: Contribution to journalArticlepeer-review

Abstract

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 Zn2+ 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 Zn2+ 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.

Original languageEnglish
Pages (from-to)15877-15882
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number44
DOIs
StatePublished - 1 Nov 2005

Keywords

  • Acetylcholine
  • Ion channel
  • Membrane protein
  • Structure

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