P2X7 receptor (P2X7)

The P2X7 receptor is a trimeric ATP-gated ion channel that belongs to the P2X receptor family and mediates purinergic signaling by allowing influx of cations such as calcium upon activation by high extracellular ATP concentrations (EC50 ≥ 1 mM).[1][2][3] Unlike other P2X subtypes, it features a unique inter-subunit hydrophobic pocket in the upper body domain that binds structurally diverse antagonists, stabilizing a closed conformation and preventing conformational changes required for channel opening, including turret narrowing and lower body domain widening.[1][2] Prolonged activation leads to pore formation permeable to molecules up to ~900 Da, triggering cell death, inflammasome activation (e.g., NLRP3), and release of inflammatory cytokines.[2][3][4] It plays key roles in immune responses, acting as a damage-associated molecular pattern (DAMP) sensor linking extracellular ATP to intracellular signaling pathways like protein kinases and phospholipases.[3][5] Dysregulation contributes to pathologies including chronic inflammation, cancer progression, neurodegenerative diseases, and atherosclerosis, positioning it as a therapeutic target for subtype-specific antagonists that exploit its distinct drug-binding pocket absent or narrower in other P2X receptors.[1][4][5][6] The term "Non-functional P2X7" does not correspond to a standard biological entity or variant in the literature; it likely refers to antagonist-bound or apo (closed-state) conformations of the wild-type P2X7 receptor that lack channel activity, as described in structural studies.[1][2] No evidence supports it as a distinct genetic loss-of-function mutant or separate target.[1][2][3]

Other names

P2Z receptor

Allosteric antagonism stabilizing closed conformation, Preventing turret narrowing and channel opening upon ATP binding