The INAD scaffold is a dynamic, redox-regulated modulator of signaling in the Drosophila eye.
Cell
; 145(7): 1088-101, 2011 Jun 24.
Article
en En
| MEDLINE
| ID: mdl-21703451
ABSTRACT
INAD is a scaffolding protein that regulates signaling in Drosophila photoreceptors. One of its PDZ domains, PDZ5, cycles between reduced and oxidized forms in response to light, but it is unclear how light affects its redox potential. Through biochemical and structural studies, we show that the redox potential of PDZ5 is allosterically regulated by its interaction with another INAD domain, PDZ4. Whereas isolated PDZ5 is stable in the oxidized state, formation of a PDZ45 "supramodule" locks PDZ5 in the reduced state by raising the redox potential of its Cys606/Cys645 disulfide bond by â¼330 mV. Acidification, potentially mediated via light and PLCß-mediated hydrolysis of PIP(2), disrupts the interaction between PDZ4 and PDZ5, leading to PDZ5 oxidation and dissociation from the TRP Ca(2+) channel, a key component of fly visual signaling. These results show that scaffolding proteins can actively modulate the intrinsic redox potentials of their disulfide bonds to exert regulatory roles in signaling.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas de Drosophila
/
Drosophila melanogaster
/
Proteínas del Ojo
Límite:
Animals
Idioma:
En
Revista:
Cell
Año:
2011
Tipo del documento:
Article
País de afiliación:
Hong Kong