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

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dc.contributor.author Martin, Renan Paulo [UNIFESP]
dc.contributor.author Rodrigues, Eliete da Silva [UNIFESP]
dc.contributor.author Corrêa, Silvana Aparecida Alves [UNIFESP]
dc.contributor.author Oliveira, Suzana Macedo [UNIFESP]
dc.contributor.author Mortara, Renato Arruda [UNIFESP]
dc.contributor.author Oliveira, Laerte [UNIFESP]
dc.contributor.author Nakaie, Clovis Ryuichi [UNIFESP]
dc.contributor.author Shimuta, Suma Imura [UNIFESP]
dc.date.accessioned 2016-01-24T14:05:33Z
dc.date.available 2016-01-24T14:05:33Z
dc.date.issued 2010-10-01
dc.identifier http://dx.doi.org/10.1515/BC.2010.117
dc.identifier.citation Biological Chemistry. Berlin: Walter de Gruyter & Co, v. 391, n. 10, p. 1189-1195, 2010.
dc.identifier.issn 1431-6730
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/32982
dc.description.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. en
dc.description.sponsorship Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorship Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent 1189-1195
dc.language.iso eng
dc.publisher Walter de Gruyter & Co
dc.relation.ispartof Biological Chemistry
dc.rights Acesso restrito
dc.subject angiotensin II en
dc.subject AT(1) receptor en
dc.subject mutant en
dc.subject SS salt bridge en
dc.title Role of the second disulfide bridge (Cys(18)-Cys(274)) in stabilizing the inactive AT(1) receptor en
dc.type Artigo
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.description.affiliation Universidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, Brazil
dc.description.affiliation Universidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, BR-04023062 São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, BR-04023062 São Paulo, Brazil
dc.description.sponsorshipID FAPESP: 07/01910-0
dc.identifier.doi 10.1515/BC.2010.117
dc.description.source Web of Science
dc.identifier.wos WOS:000283654500009



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