Role of the second disulfide bridge (Cys(18)-Cys(274)) in stabilizing the inactive AT(1) receptor

Role of the second disulfide bridge (Cys(18)-Cys(274)) in stabilizing the inactive AT(1) receptor

Author Martin, Renan Paulo Autor UNIFESP Google Scholar
Rodrigues, Eliete da Silva Autor UNIFESP Google Scholar
Corrêa, Silvana Aparecida Alves Autor UNIFESP Google Scholar
Oliveira, Suzana Macedo Autor UNIFESP Google Scholar
Mortara, Renato Arruda Autor UNIFESP Google Scholar
Oliveira, Laerte Autor UNIFESP Google Scholar
Nakaie, Clovis Ryuichi Autor UNIFESP Google Scholar
Shimuta, Suma Imura Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract Previous research showed that disruption of the Cys(18)-Cys(274) bond in the angiotensin II (AngII) AT(1) receptor mutant (C18S), expressed in CHO cells, causes an increase in the basal activity and attenuation of the maximum response to AngII. in addition, this mutant was mostly intracellularly distributed. Our aim was to investigate whether the intracellular presence of the mutant was due to a constitutive internalization or to a defective maturation of the receptor. the first hypothesis was assessed by pretreating the cells with losartan or [Sar(1)Leu(8)]-AngII, specific AT(1) receptor antagonists, a maneuver to revert the receptor internalization. the second hypothesis was tested using calnexin, an endoplasmic reticulum marker. We found that treatment with AT(1) receptor antagonists causes an increase in the binding ability of the mutant to AngII. Furthermore, whereas the maximum effect is increased, it reduces the enhanced basal levels of IP3. the hypothesis for a lack of maturation of the mutant receptor was ruled out because calnexin was poorly colocalized with the intracellular C18S receptor. Our results suggest that the mutation of the AT(1) receptor leads to a conformational structure similar to that of the active mode of the AT(1) receptor, favoring its internalization in the absence of the agonist.
Keywords angiotensin II
AT(1) receptor
mutant
SS salt bridge
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 07/01910-0
Date 2010-10-01
Published in Biological Chemistry. Berlin: Walter de Gruyter & Co, v. 391, n. 10, p. 1189-1195, 2010.
ISSN 1431-6730 (Sherpa/Romeo, impact factor)
Publisher Walter de Gruyter & Co
Extent 1189-1195
Origin http://dx.doi.org/10.1515/BC.2010.117
Access rights Closed access
Type Article
Web of Science ID WOS:000283654500009
URI http://repositorio.unifesp.br/handle/11600/32982

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