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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

Full text
Author(s):
Martin, Renan Paulo [1] ; Rodrigues, Eliete da Silva [1] ; Alves Correa, Silvana Aparecida [1] ; Oliveira, Suzana Macedo [1] ; Mortara, Renato Arruda [2] ; Oliveira, Laerte [1] ; Nakaie, Clovis Ryuichi [1] ; Shimuta, Suma Imura [1]
Total Authors: 8
Affiliation:
[1] Univ Fed Sao Paulo, Dept Biophys, BR-04023062 Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, BR-04023062 Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Biological Chemistry; v. 391, n. 10, p. 1189-1195, OCT 2010.
Web of Science Citations: 2
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 IP(3). 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. (AU)

FAPESP's process: 07/01910-0 - Identification of different binding modes of Angiotensin II N-terminal domain with wild-type and mutant AT1 receptors
Grantee:Renan Paulo Martin
Support Opportunities: Scholarships in Brazil - Master