Structural insights into the nucleotide base specificity of P2X receptors.
Sci Rep
; 7: 45208, 2017 03 23.
Article
en En
| MEDLINE
| ID: mdl-28332633
ABSTRACT
P2X receptors are trimeric ATP-gated cation channels involved in diverse physiological processes, ranging from muscle contraction to nociception. Despite the recent structure determination of the ATP-bound P2X receptors, the molecular mechanism of the nucleotide base specificity has remained elusive. Here, we present the crystal structure of zebrafish P2X4 in complex with a weak affinity agonist, CTP, together with structure-based electrophysiological and spectroscopic analyses. The CTP-bound structure revealed a hydrogen bond, between the cytosine base and the side chain of the basic residue in the agonist binding site, which mediates the weak but significant affinity for CTP. The cytosine base is further recognized by two main chain atoms, as in the ATP-bound structure, but their bond lengths seem to be extended in the CTP-bound structure, also possibly contributing to the weaker affinity for CTP over ATP. This work provides the structural insights for the nucleotide base specificity of P2X receptors.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Citidina Trifosfato
/
Proteínas de Pez Cebra
/
Receptores Purinérgicos P2X
Límite:
Animals
Idioma:
En
Revista:
Sci Rep
Año:
2017
Tipo del documento:
Article
País de afiliación:
Japón