Histidine 140 plays a key role in the inhibitory modulation of the P2X<sub>4</sub> nucleotide receptor by copper but not zinc

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dc.contributor.authorCoddou, C
dc.contributor.authorMorales, B
dc.contributor.authorGonzález, J
dc.contributor.authorGrauso, M
dc.contributor.authorGordillo, F
dc.contributor.authorBull, P
dc.contributor.authorRassendren, F
dc.contributor.authorHuidobro-Toro, JP
dc.date.accessioned2025-01-21T01:08:57Z
dc.date.available2025-01-21T01:08:57Z
dc.date.issued2003
dc.description.abstractTo elucidate the role of extracellular histidines in the modulation of the rat P2X(4) receptor by trace metals, we generated single, double, and triple histidine mutants for residues 140, 241, and 286, replacing them with alanines. cDNAs for the wild-type and receptor mutants were expressed in Xenopus laevis oocytes and in human embryonic kidney 293 cells and examined by the two electrode and patch clamp techniques, respectively. Whereas copper inhibited concentration-dependently the ATP-gated currents in the wild-type and in the single or double H241A and H286A receptor mutants, all receptors containing H140A were insensitive to copper in both cell systems. The characteristic bell-shaped concentration-response curve of zinc observed in the wildtype receptor became sigmoid in both oocytes and human embryonic kidney cells expressing the H140A mutant; in these mutants, the zinc potentiation was 2.5-4-fold larger than in the wild-type. Results with the H140T and H140R mutants further support the importance of a histidine residue at this position. We conclude that His-140 is critical for the action of copper, indicating that this histidine residue, but not His-241 or His-286, forms part of the inhibitory allosteric metal-binding site of the P2X4 receptor, which is distinct from the putative zinc facilitator binding site.
dc.fuente.origenWOS
dc.identifier.doi10.1074/jbc.M305177200
dc.identifier.eissn1083-351X
dc.identifier.issn0021-9258
dc.identifier.urihttps://doi.org/10.1074/jbc.M305177200
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/96529
dc.identifier.wosidWOS:000185318300110
dc.issue.numero38
dc.language.isoen
dc.pagina.final36785
dc.pagina.inicio36777
dc.revistaJournal of biological chemistry
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleHistidine 140 plays a key role in the inhibitory modulation of the P2X<sub>4</sub> nucleotide receptor by copper but not zinc
dc.typeartículo
dc.volumen278
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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