2012
DOI: 10.1038/emboj.2012.75
|View full text |Cite
|
Sign up to set email alerts
|

Tightening of the ATP-binding sites induces the opening of P2X receptor channels

Abstract: 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' indu… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1

Citation Types

11
95
0

Year Published

2013
2013
2022
2022

Publication Types

Select...
5
2

Relationship

0
7

Authors

Journals

citations
Cited by 77 publications
(108 citation statements)
references
References 56 publications
(106 reference statements)
11
95
0
Order By: Relevance
“…For example, ATP binding to the cleft and subsequent cleft closure were predicted to occur based on proximity tethering (11), normal mode analysis (12), and both metal bridging and spectroscopic studies (13,14). In addition, the accessibility of both methanethiolsulfonate compounds and metals (Ag + and Cd 2+ ) to cysteine residues introduced into TM1 and TM2 (6)(7)(8) is consistent with the expansion of the external pore predicted from the zfP2X4 structures (Fig.…”
supporting
confidence: 58%
“…For example, ATP binding to the cleft and subsequent cleft closure were predicted to occur based on proximity tethering (11), normal mode analysis (12), and both metal bridging and spectroscopic studies (13,14). In addition, the accessibility of both methanethiolsulfonate compounds and metals (Ag + and Cd 2+ ) to cysteine residues introduced into TM1 and TM2 (6)(7)(8) is consistent with the expansion of the external pore predicted from the zfP2X4 structures (Fig.…”
supporting
confidence: 58%
“…Those conformational changes are distinct from previously identified allosteric events essential for channel activations, such as the downward motion of cysteine-rich head domain, tightening of the ATP-binding site jaw and the upper vestibule expansions 5,6,8,9 . As revealed by the spontaneous closure of the ATP-binding site jaw (Fig.…”
Section: Discussionmentioning
confidence: 94%
“…1c and Supplementary Movie 1). Those structural changes are widely accepted to associate with channel opening [6][7][8]10 . Nevertheless, a comparison of pore size of the initial and representative conformation after MD simulations (Fig.…”
Section: Structural Dynamics Of Lf and Df Domains During Simulationsmentioning
confidence: 99%
See 2 more Smart Citations