Conserved Negatively Charged Residues Are Not Required for ATP Action at P2X1 Receptors

Ennion, Steven J.; Ritson, Jonathan; Evans, Richard J.

doi:10.1006/bbrc.2001.6034

Cited by 21 publications

(17 citation statements)

References 13 publications

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“…By complexing ATP, Mg 2ϩ and Ca 2ϩ may influence binding of ATP to purinergic receptors. However, in the case of P2X(1) receptors, alanine substitution mutagenesis studies indicate that coordinated binding of the positive charge on magnesium-complexed ATP by negatively charged amino acids is not required for activation of the receptor by ATP (Ennion et al, 2001). Since hydrolysis of ATP by ectoATPases may be dependent on divalent cations (Nagy et al, 1986;Hohmann et al, 1993), [Mg 2ϩ ] o and [Ca 2ϩ ] o could also influence extracellular purinergic signaling in this manner.…”

Section: Discussionmentioning

confidence: 99%

Modulation of intercellular calcium signaling in astrocytes by extracellular calcium and magnesium

Stout

Charles

2003

Glia

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The extracellular concentrations of Ca 2ϩ and Mg 2ϩ are well known to play important roles in the function of the central nervous system. We examined the effects of extracellular Ca 2ϩ and Mg 2ϩ on ATP release and intercellular signaling in astrocytes. [Ca 2ϩ ] o -activated whole cell currents consistent with currents through connexin hemichannels. These currents were inhibited by extracellular Mg 2ϩ . We conclude that extracellular divalent cations modulate intercellular Ca 2ϩ signaling in astrocytes by modulating the release of ATP, possibly via connexin hemichannels.

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Section: Discussionmentioning

confidence: 99%

Modulation of intercellular calcium signaling in astrocytes by extracellular calcium and magnesium

Stout

Charles

2003

Glia

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“…It is assumed that ATP forms complexes with Mg 2+ (Ashcroft and Gribble, 1998; Ennion et al, 2001; Li et al, 2013). For this reason, it has been postulated that the negatively charged amino acids of P2X receptors could contribute to the binding of ATP (Ennion et al, 2001).…”

Section: Mutagenesis-based Analysis Of Atp Binding Site: a Comparisonmentioning

confidence: 99%

Exploring the ATP-binding site of P2X receptors

Chataigneau

Lemoine

Grütter

2013

Front. Cell. Neurosci.

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P2X receptors are ATP-gated non-selective cation channels involved in many different physiological processes, such as synaptic transmission, inflammation, and neuropathic pain. They form homo- or heterotrimeric complexes and contain three ATP-binding sites in their extracellular domain. The recent determination of X-ray structures of a P2X receptor solved in two states, a resting closed state and an ATP-bound, open-channel state, has provided unprecedented information not only regarding the three-dimensional shape of the receptor, but also on putative conformational changes that couple ATP binding to channel opening. These data provide a structural template for interpreting the huge amount of functional, mutagenesis, and biochemical data collected during more than fifteen years. In particular, the interfacial location of the ATP binding site and ATP orientation have been successfully confirmed by these structural studies. It appears that ATP binds to inter-subunit cavities shaped like open jaws, whose tightening induces the opening of the ion channel. These structural data thus represent a firm basis for understanding the activation mechanism of P2X receptors.

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“…Thus, it seemed likely that as for other ATP binding proteins, conserved charged residues in the P2X receptor could be important in coordinating the action of ATP. The contribution of conserved charged residues was determined in both human P2X 1 and rat P2X 2 receptor backgrounds [46,101,105]. These showed that mutation of positively charged lysine (K) and arginine (R) residues K68, K70, R292 and K309 (P2X 1 receptor numbering) resulted in a large decrease (up to a 1,000-fold decrease for K68A) in ATP potency at the receptor, suggesting that these residues play a role in the coordination of the negatively charged phosphate group of ATP.…”

Section: Drug Action At P2x Receptorsmentioning

confidence: 99%

Molecular properties of P2X receptors

Roberts

Vial

Digby

et al. 2006

Pflugers Arch - Eur J Physiol

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158

142

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P2X receptors for adenosine tri-phosphate (ATP) are a distinct family of ligand-gated cation channels with two transmembrane domains, intracellular amino and carboxy termini and a large extracellular ligand binding loop. Seven genes (P2X(1-7)) have been cloned and the channels form as either homo or heterotrimeric channels giving rise to a wide range of phenotypes. This review aims to give an account of recent work on the molecular basis of the properties of P2X receptors. In particular, to consider emerging information on the assembly of P2X receptor subunits, channel regulation and desensitisation, targeting, the molecular basis of drug action and the functional contribution of P2X receptors to physiological processes.

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Conserved Negatively Charged Residues Are Not Required for ATP Action at P2X1 Receptors

Cited by 21 publications

References 13 publications

Modulation of intercellular calcium signaling in astrocytes by extracellular calcium and magnesium

Modulation of intercellular calcium signaling in astrocytes by extracellular calcium and magnesium

Exploring the ATP-binding site of P2X receptors

Molecular properties of P2X receptors

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