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Tightening of the ATP‐binding sites induces the opening of P2X receptor channels
Author(s) -
Jiang Ruotian,
Taly Antoine,
Lemoine Damien,
Martz Adeline,
Cunrath Olivier,
Grutter Thomas
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2012.75
Subject(s) - biology , binding site , receptor , microbiology and biotechnology , plasma protein binding , biophysics , adenosine triphosphate , genetics , biochemistry
The opening of ligand‐gated ion channels in response to agonist binding is a fundamental process in biology. In ATP‐gated P2X receptors, little is known about the molecular events that couple ATP binding to channel opening. In this paper, we identify structural changes of the ATP site accompanying the P2X2 receptor activation by engineering extracellular zinc bridges at putative mobile regions as revealed by normal mode analysis. We provide evidence that tightening of the ATP sites shaped like open ‘jaws’ induces opening of the P2X ion channel. We show that ATP binding favours jaw tightening, whereas binding of a competitive antagonist prevents gating induced by this movement. Our data reveal the inherent dynamic of the binding jaw, and provide new structural insights into the mechanism of P2X receptor activation.