Related Experiment Video

Updated: Jun 25, 2026

Proteomics to Identify Proteins Interacting with P2X2 Ligand-Gated Cation Channels
16:36

Proteomics to Identify Proteins Interacting with P2X2 Ligand-Gated Cation Channels

Published on: May 18, 2009

Activation of the P2X7 ion channel by soluble and covalently bound ligands

Nicole Schwarz1, Ralf Fliegert, Sahil Adriouch

  • 1Institute of Immunology, Campus-Forschung 02.059, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.

Purinergic Signalling
|March 4, 2009
PubMed

Insights

The P2X7 receptor senses adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD). Arginine mutations reveal how NAD binding, via ADP-ribosylation at R125, activates the P2X7 receptor.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Signaling

Background:

  • The P2X7 receptor is a homotrimeric purinergic receptor that responds to extracellular ATP and NAD.
  • It plays a role in calcium signaling and cell death pathways.
  • Understanding its ligand-binding mechanism is crucial for therapeutic development.

Purpose of the Study:

  • To investigate the role of arginine residues in the P2X7 receptor's response to ligands.
  • To elucidate the mechanism by which nicotinamide adenine dinucleotide (NAD) activates the P2X7 receptor.

Main Methods:

  • Site-directed mutagenesis of arginine residues in the P2X7 receptor.
  • Assays to measure receptor activation by soluble and covalently bound ligands.
  • Analysis of ADP-ribosylation at specific sites.

Main Results:

  • High concentrations of extracellular ATP activate P2X7 as a soluble ligand.
  • Low concentrations of extracellular NAD activate P2X7 after ADP-ribosylation at R125, catalyzed by ART2.2.
  • ADP-ribosylation at R125 likely positions the adenine moiety of NAD within the P2X7 ligand-binding pocket.

Conclusions:

  • The P2X7 receptor's activation mechanism involves distinct responses to ATP and NAD.
  • Residue R125 is critical for NAD-mediated activation through ADP-ribosylation.
  • This study provides insights into the molecular basis of P2X7 receptor gating by purinergic ligands.

More Related Videos

Real-time Live-cell Flow Cytometry to Investigate Calcium Influx, Pore Formation, and Phagocytosis by P2X7 Receptors in Adult Neural Progenitor Cells11:47

Real-time Live-cell Flow Cytometry to Investigate Calcium Influx, Pore Formation, and Phagocytosis by P2X7 Receptors in Adult Neural Progenitor Cells

Published on: April 3, 2019

Related Concept Videos

Ligand-gated Ion Channels01:19

Ligand-gated Ion Channels

Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...
Ligand-gated Ion Channels01:19

Ligand-gated Ion Channels

Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...
Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
Ion Channels01:19

Ion Channels

The movement of ions like sodium, potassium, and calcium into and out of the cell is essential to maintain the electrochemical gradient in living cells. The ion channels—a class of membrane transport proteins—help maintain this ionic gradient for the smooth functioning of physiological activities such as maintaining cell size and volume, conducting nerve impulses, and gas and nutrient exchange.
Ion channels are specialized integral membrane proteins on the plasma membrane that allow specific...
Mechanically-gated Ion Channels01:12

Mechanically-gated Ion Channels

Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
Signal Transduction: Overview01:26

Signal Transduction: Overview

Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...