Structural analysis of three peptides related to the transmambranic helix VI of AT1 receptor

Structural analysis of three peptides related to the transmambranic helix VI of AT1 receptor

Autor Ribeiro de Noronha, Samuel Marcos Autor UNIFESP Google Scholar
Corrêa, Silvana Aparecida Alves Autor UNIFESP Google Scholar
Poletti, Erick Fernando Google Scholar
Lopes, Douglas Duarte Google Scholar
Silva, Caroline Correa da Google Scholar
Sforca, Mauricio Luis Google Scholar
Shimuta, Suma Imura Google Scholar
Tonin Zanchin, Nilson Ivo Google Scholar
Nakaie, Clovis Ryuichi Google Scholar
Cotrim Guerreiro da Silva, Ismael Dale Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Dept Biofis
Lab Nacl Luz Sincroton
Resumo Introduction: Angiotensin II (AII) is the main active product of the renin angiotensin system. Better known effects of All are via AT1 receptor (AT1R). Expression of AT1R mutants (L265D and L262D) in CHO cells increased cAMP formation when compared to CHO cells expressing the wild type (WT) AT1R. Morphological transformation of CHO cells transfected with mutants correlated with their increased cAMP formation. DNA synthesis was inhibited in these cells too, indicating that cAMP promotes inhibitory effects on transfected CHO cells growth and causes their morphological change from a tumorigenic phenotype to a non-tumorigenic one.Objectives: To assess the importance of leucine 262 and 265 in determining AT1R structure by means of a comparative structural analysis of two mutant peptides and of a wild-type fragment.Methodology: Three peptides had their conformation compared by circular dichroism (CD): L262D(259-272). L265D(259-272) (mutants) and WT(260-277).Results: Secondary structures were: beta-turn for WT and L262D and random coil for L265D.Conclusions: Strong correlation was found in the results of biochemical, cellular and structural approaches used to compare WT AT1R to mutant types. Random coil structure of the L265D mutant may be a key point to explain those changes observed in biochemical (binding and signal transduction) and proliferation assays (Correa et al., 2005). beta-Turn formation is an important step during early protein folding and this secondary simple structure is present in L262D and WT, but not in L265D. Therefore, leucine 265 seems to play a crucial role in determining an entirely functional AT1R. (C) 2009 Elsevier B.V. All rights reserved.
Assunto Angiotensin II type 1 receptor
Angiotensin II
Renin angiotensin system
Circular dichroism spectroscopy
Idioma Inglês
Data 2010-04-01
Publicado em Neuropeptides. Edinburgh: Churchill Livingstone, v. 44, n. 2, p. 115-118, 2010.
ISSN 0143-4179 (Sherpa/Romeo, fator de impacto)
Editor Churchill Livingstone
Extensão 115-118
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000276001700008

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