Size matters in activation/inhibition of ligand-gated ion channels.

Abstract:

:Cys loop, glutamate, and P2X receptors are ligand-gated ion channels (LGICs) with 5, 4, and 3 protomers, respectively. There is now growing atomic level understanding of their gating mechanisms. Although each family is unique in the architecture of the ligand-binding pocket, the pathway for motions to propagate from ligand-binding domain to transmembrane domain, and the gating motions of the transmembrane domain, there are common features among the LGICs, which are the focus of the present review. In particular, agonists and competitive antagonists apparently induce opposite motions of the binding pocket. A simple way to control the motional direction is ligand size. Agonists, usually small, induce closure of the binding pocket, leading to opening of the channel pore, whereas antagonists, usually large, induce opening of the binding pocket, thereby stabilizing the closed pore. A cross-family comparison of the gating mechanisms of the LGICs, focusing in particular on the role played by ligand size, provides new insight on channel activation/inhibition and design of pharmacological compounds.

journal_name

Trends Pharmacol Sci

authors

Du J,Dong H,Zhou HX

doi

10.1016/j.tips.2012.06.005

subject

Has Abstract

pub_date

2012-09-01 00:00:00

pages

482-93

issue

9

eissn

0165-6147

issn

1873-3735

pii

S0165-6147(12)00093-4

journal_volume

33

pub_type

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