Fiche publication
Date publication
juillet 2019
Journal
The Journal of general physiology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GRUTTER Thomas
Tous les auteurs :
Gasparri F, Wengel J, Grutter T, Pless SA
Lien Pubmed
Résumé
P2X receptors (P2XRs) are trimeric ligand-gated ion channels that open a cation-selective pore in response to ATP binding. P2XRs contribute to synaptic transmission and are involved in pain and inflammation, thus representing valuable drug targets. Recent crystal structures have confirmed the findings of previous studies with regards to the amino acid chains involved in ligand recognition, but they have also suggested that backbone carbonyl atoms contribute to ATP recognition and discrimination. Here we use a combination of site-directed mutagenesis, amide-to-ester substitutions, and a range of ATP analogues with subtle alterations to either base or sugar component to investigate the contributions of backbone carbonyl atoms toward ligand recognition and discrimination in rat P2X2Rs. Our findings demonstrate that while the Lys69 backbone carbonyl makes an important contribution to ligand recognition, the discrimination between different ligands is mediated by both the side chain and the backbone carbonyl oxygen of Thr184. Together, our data demonstrate how conserved elements in P2X2Rs recognize and discriminate agonists.
Mots clés
Amino Acid Substitution, Animals, Binding Sites, HEK293 Cells, Humans, Protein Binding, Purinergic P2X Receptor Agonists, chemistry, Receptors, Purinergic P2X2, chemistry, Xenopus laevis
Référence
J Gen Physiol. 2019 07 1;151(7):898-911
