Essential role of TM V and VI for binding the C-terminal sequences of Des-Arg-kinins

Essential role of TM V and VI for binding the C-terminal sequences of Des-Arg-kinins

Author Santos, Edson L. Autor UNIFESP Google Scholar
Souza, Kely de Picoli Autor UNIFESP Google Scholar
Cibrian-Uhatte, Elena Google Scholar
Oliveira, Suzana M. Autor UNIFESP Google Scholar
Bader, Michael Google Scholar
Costa-Neto, Claudio M. Google Scholar
Oliveira, Laerte Autor UNIFESP Google Scholar
Pesquero, Joao B. Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Max Delbruck Ctr Mol Med
Abstract In the kallikrein-kinin and renin-angiotensin systems the main receptors, B-1 and B-2 (kinin receptors) and AT(1) and AT(2) (angiotensin receptors) respectively, are seven-transmembrane domain G-protein-coupled receptors. Considering that the B, agonists Des-Arg(9)-BK (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe), Lys-desArg(9)-BK or Des-Arg(10)-KD (Lys-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe) and the AT, agonist (Asp-Arg-Val-Tyr-lle-His-Pro-Phe) have the same two residues at the C-terminal region (i.e. Pro-Phe), we hypothesized that TM V and TM VI of the B-1 receptor could play an essential role in agonist binding and activity, being these regions receptor sites for binding the C-terminal sequences of Des-Arg-kinins similarly to that observed to AT, receptor. To investigate this hypothesis, we replaced Arg(212) for Ala at the top of the TM V and the sequence 274-282 (CPYHFFAFL) in TM VI of the rat kinin B, receptor by the 32 receptor homologous sequence, 289-297 (FPFQISTFL) and subsequently analyzed the consequences of these mutations by competition binding and functional assays. Despite correct expression, observed at the mRNA and protein level by RT-PCR and confocal microscopy, respectively, no agonist binding and function was verified for the mutated receptors. Therefore, our results suggest an important role for Arg(212) in the TM V and a region of TM VI of rat B, receptor in the interaction with the C-terminal residues of Des-Arg-kinins, similar to that observed with AngII. (c) 2007 Elsevier B.V. All rights reserved.
Keywords mutagenesis
kinin B-1 receptor
G-protein-coupled receptors
Language English
Date 2008-02-01
Published in International Immunopharmacology. Amsterdam: Elsevier B.V., v. 8, n. 2, p. 282-288, 2008.
ISSN 1567-5769 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 282-288
Access rights Closed access
Type Article
Web of Science ID WOS:000253025700027

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