Cutting edge: The nucleotide receptor P2X(7) contains multiple protein- and lipid-interaction motifs including a potential binding site for bacteriallipopolysaccharide

The nucleotide receptor P2X(7) has been shown to modulate LPS-induced macro phage production of numerous inflammatory mediators. Although the C-termina l portion of P2X7 is thought to be essential for multiple receptor function s, little is known regarding the structural motifs that lie within this reg ion. We show here that the P2X7 C-terminal domain contains several apparent protein-protein and protein-lipid interaction motifs with potential import ance to macrophage signaling and LPS action. Surprisingly, P2X7 also contai ns a conserved LPS-binding domain. In this report, we demonstrate that pept ides derived from this P2X7 sequence bind LPS in vitro. Moreover, these pep tides neutralize the ability of LPS to activate the extracellular signal-re gulated kinases (ERK1, ERK2) and to promote the degradation of the inhibito r of kappa beta-alpha isoform (I kappa beta-alpha) in RAW 264.7 macrophages . Collectively, these data suggest that the C-terminal domain of P2X7 may d irectly coordinate several signal transduction events related to macrophage unction and LPS action.