ADP-ribosylation at R125 gates the P2X7 ion channel by presenting a covalent ligand to its nucleotide binding site.
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ADP-ribosylation at R125 gates the P2X7 ion channel by presenting a covalent ligand to its nucleotide binding site. / Adriouch, Sahil; Bannas, Peter; Schwarz, Nicole; Fliegert, Ralf; Guse, Andreas H.; Seman, Michel; Haag, Friedrich; Koch Nolte, Friedrich.
In: FASEB J, Vol. 22, No. 3, 3, 2008, p. 861-869.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - ADP-ribosylation at R125 gates the P2X7 ion channel by presenting a covalent ligand to its nucleotide binding site.
AU - Adriouch, Sahil
AU - Bannas, Peter
AU - Schwarz, Nicole
AU - Fliegert, Ralf
AU - Guse, Andreas H.
AU - Seman, Michel
AU - Haag, Friedrich
AU - Koch Nolte, Friedrich
PY - 2008
Y1 - 2008
N2 - ADP-ribosylation is a post-translational modification regulating protein function in which amino acid-specific ADP-ribosyltransferases (ARTs) transfer ADP-ribose from NAD onto specific target proteins. Attachment of the bulky ADP-ribose usually inactivates the target by sterically blocking its interaction with other proteins. P2X7, an ATP-gated ion channel with important roles in inflammation and cell death, in contrast, is activated by ADP-ribosylation. Here, we report the structural basis for this gating and present the first molecular model for the activation of a target protein by ADP-ribosylation. We demonstrate that the ecto-enzyme ART2.2 ADP-ribosylates P2X7 at arginine 125 in a prominent, cysteine-rich region at the interface of 2 receptor subunits. ADP-ribose shares an adenine-ribonucleotide moiety with ATP. Our results indicate that ADP-ribosylation of R125 positions this common chemical framework to fit into the nucleotide-binding site of P2X7 and thereby gates the channel.
AB - ADP-ribosylation is a post-translational modification regulating protein function in which amino acid-specific ADP-ribosyltransferases (ARTs) transfer ADP-ribose from NAD onto specific target proteins. Attachment of the bulky ADP-ribose usually inactivates the target by sterically blocking its interaction with other proteins. P2X7, an ATP-gated ion channel with important roles in inflammation and cell death, in contrast, is activated by ADP-ribosylation. Here, we report the structural basis for this gating and present the first molecular model for the activation of a target protein by ADP-ribosylation. We demonstrate that the ecto-enzyme ART2.2 ADP-ribosylates P2X7 at arginine 125 in a prominent, cysteine-rich region at the interface of 2 receptor subunits. ADP-ribose shares an adenine-ribonucleotide moiety with ATP. Our results indicate that ADP-ribosylation of R125 positions this common chemical framework to fit into the nucleotide-binding site of P2X7 and thereby gates the channel.
M3 - SCORING: Zeitschriftenaufsatz
VL - 22
SP - 861
EP - 869
JO - FASEB J
JF - FASEB J
SN - 0892-6638
IS - 3
M1 - 3
ER -
