Residues Val(254), His(256), and Phe(259) of the angiotensin II AT(1) receptor are not involved in ligand binding but participate in signal transduction

• Autor(a) principal: Han, Heliana Maria do Carmo Barbosa [UNIFESP]
• Data de Publicação: 1998
• Outros Autores: Shimuta, Suma Imura [UNIFESP], Kanashiro, Celia Akemi [UNIFESP], Oliveira, Laerte [UNIFESP], Han, Sang Won [UNIFESP], Paiva, Antonio Cechelli de Mattos [UNIFESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• dARK ID: ark:/48912/001300000jxhd
• DOI: 10.1210/mend.12.6.0127
• Texto Completo: http://dx.doi.org/10.1210/mend.12.6.0127; http://repositorio.unifesp.br/handle/11600/25899

The role of the external third of helix VI of the angiotensin II (AII) AT(1) receptor for the interaction with its ligand and for the subsequent signal transduction was investigated by individually replacing residues 252-256 by Ala, and residues 259 or 261 by Tyr, and permanently transfecting the resulting mutants to Chinese hamster ovary (CHO) cells, Binding experiments showed no great changes in affinity of any of the mutants for AII, [Sar(1)]-AII, or [Sar(1), Leu(8)]-AII, but the affinity for the nonpeptide antagonist DuP753 was significantly decreased. the inositol phosphate response to AII was remarkably decreased in mutants V254A, H256A, and F259Y. These results indicate that AT(1) residues Val(254), His(256), and Phe(259) are not involved in ligand binding but participate in signal transduction, Based in these results and in others from the literature, it is suggested that, in addition tea the His(256) imidazole ring, the Phe(259) aromatic ring interacts with the AII's Phe(8), thus contributing to the signal-triggering mechanism.