2010
DOI: 10.1074/jbc.m110.101980
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A Putative Extracellular Salt Bridge at the Subunit Interface Contributes to the Ion Channel Function of the ATP-gated P2X2 Receptor

Abstract: The recent crystal structure of the ATP-gated P2X4 receptor revealed a static view of its architecture, but the molecular mechanisms underlying the P2X channels activation are still unknown. By using a P2X2 model based on the x-ray structure, we sought salt bridges formed between charged residues located in a region that directly connects putative ATP-binding sites to the ion channel. To reveal their significance for ion channel activation, we made systematic charge exchanges and measured the effects on ATP se… Show more

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Cited by 46 publications
(72 citation statements)
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“…The holding potential was −60 mV. Dose-response relationship experiments and drug applications were carried out as described previously (5). The apparent reaction rate constant k app was determined by fitting data with a single exponential equation.…”
Section: Methodsmentioning
confidence: 99%
See 1 more Smart Citation
“…The holding potential was −60 mV. Dose-response relationship experiments and drug applications were carried out as described previously (5). The apparent reaction rate constant k app was determined by fitting data with a single exponential equation.…”
Section: Methodsmentioning
confidence: 99%
“…Upon ATP binding, structural rearrangements of the subunit interface (3)(4)(5) lead to the opening of the ion channel (6)(7)(8), but the entire molecular sequence of events that couple ATP binding to channel opening remains unknown. The recent X-ray structure of the P2X4 receptor in a closed resting state represents in this regard a decisive step (9).…”
mentioning
confidence: 99%
“…These findings confirm the essential role of the lower body domain in conformational transitions during channel gating. D197 (rat P2X7, rP2X7 numbering), located in the lower body domain, is pivotal for acidic pH-induced channel inhibition [80] , suggesting an additional function of the lower body domain that is independent to the movement of the LF and DF domains, and this was confirmed by the importance of the salt bridge E63-R274 (rP2X2 numbering) in this domain for the channel gating [81] . Actually, both the closure of binding site jaw and the movement of the lower body domain are required for the concomitant pore opening of P2X receptors [33] .…”
Section: Lower Body Domainmentioning
confidence: 62%
“…Previous studies demonstrated that the ion channel function could be restored by charge swapping or disulfide trapping of the salt bridge in some receptors (31,32,35). Here, disruption of the salt bridge by charge reversal at one amino acid of the salt bridge attenuated ATP-induced maximum currents (I max ϭ 5.46 Ϯ 2.6 and 2.69 Ϯ 0.7 pA/pF, for R309D and D85R, respectively; n ϭ 6 -10; Fig.…”
Section: Salt Bridge Between Arg-309 and Asp-85 Is A Stringent Structmentioning
confidence: 92%