ATP binding at human P2X1 receptors. Contribution of aromatic and basic amino acids revealed using mutagenesis and partial agonists

P2X receptors comprise a family of ATP-gated ion channels with the basic amino acids Lys-68, Arg-292, and Lys-309 (P2X(1) receptor numbering) contributing to agonist potency. In many ATP-binding proteins aromatic amino acids coordinate the binding of the adenine group. There are 20 conserved aromati...

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Bibliographic Details
Published in:The Journal of biological chemistry 2004-03, Vol.279 (10), p.9043
Main Authors: Roberts, Jonathan A, Evans, Richard J
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - analogs & derivatives
Adenosine Triphosphate - metabolism
Adenosine Triphosphate - pharmacology
Amino Acid Sequence
Animals
Binding Sites - genetics
Humans
Ion Channel Gating
Ligands
Molecular Sequence Data
Mutagenesis, Site-Directed
Protein Binding
Purinergic P2 Receptor Agonists
Receptors, Purinergic P2 - genetics
Receptors, Purinergic P2 - metabolism
Receptors, Purinergic P2X
Sequence Alignment
Xenopus laevis
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Summary:P2X receptors comprise a family of ATP-gated ion channels with the basic amino acids Lys-68, Arg-292, and Lys-309 (P2X(1) receptor numbering) contributing to agonist potency. In many ATP-binding proteins aromatic amino acids coordinate the binding of the adenine group. There are 20 conserved aromatic amino acids in the extracellular ligand binding loop of at least 6 of the 7 P2X receptors. We used alanine replacement mutagenesis to determine the effects of individual conserved aromatic residues on the properties of human P2X(1) receptors expressed in Xenopus oocytes. ATP evoked concentration-dependent (EC(50) approximately 1 microm) desensitizing currents at wild-type receptors and for the majority of mutants there was no change (10 residues) or a
ISSN:0021-9258
DOI:10.1074/jbc.M308964200