A role for transmembrane domains V and VI in ligand binding and maturation of the angiotensin II AT1 receptor

A role for transmembrane domains V and VI in ligand binding and maturation of the angiotensin II AT1 receptor

Autor Pignatari, G. C. Google Scholar
Rozenfeld, R. Google Scholar
Ferro, E. S. Google Scholar
Oliveira, L. Google Scholar
Paiva, ACM Google Scholar
Devi, L. A. Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
CUNY Mt Sinai Sch Med
Universidade de São Paulo (USP)
Resumo Several studies have proposed that angiotensin II (Ang II) binds to its receptor AT1 through interactions with residues in helices V and VI, suggesting that the distance between these helices is crucial for ligand binding. Based on a 3D model of AT1 in which the C-terminus of Ang II is docked, we identified the hydrophobic residues of TM V and VI pointing towards the external face of the helices, which may play a role in the structure of the binding pocket and in the structural integrity of the receptor. We performed a systematic mutagenesis study of these residues and examined the binding, localization, maturation, and dimerization of the mutated receptors. We found that mutations of hydrophobic residues to alanine in helix V do not alter binding, whereas mutations to glutamate lead to loss of binding without a loss in cell surface expression, suggesting that the external face of helix V may not directly participate in binding, but may rather contribute to the structure of the binding pocket. in contrast, mutations of hydrophobic residues to glutamate in helix VI lead to a loss in cell surface expression, suggesting that the external surface of helix VI plays a structural role and ensures correct folding of the receptor.
Palavra-chave dimerization
folding
GPCR
maturation
site-directed mutagenesis
Idioma Inglês
Data de publicação 2006-03-01
Publicado em Biological Chemistry. Berlin: Walter de Gruyter & Co, v. 387, n. 3, p. 269-276, 2006.
ISSN 1431-6730 (Sherpa/Romeo, fator de impacto)
Publicador Walter de Gruyter & Co
Extensão 269-276
Fonte http://dx.doi.org/10.1515/BC.2006.036
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000236202900006
Endereço permanente http://repositorio.unifesp.br/handle/11600/28788

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