Relationships between structure and activity of receptors coupled to G proteins: vasoactive peptide receptors

• Grant number: 95/04642-7
• Support Opportunities: Research Projects - Thematic Grants
• Start date: March 01, 1996
• End date: January 31, 2001
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Antonio Cechelli de Mattos Paiva
• Grantee: Antonio Cechelli de Mattos Paiva
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant(s): 99/04036-0 - A ligand common site im g-protein coupled receptors., AR.EXT; 98/07500-7 - "residues val254, his256 and phe259 of the angiotensin ii at1 receptor are not involved in ligand binding..."., PUB.ART; 97/07122-0 - Residues VAL 254, his 256 and PHE 259 of the Angiotensin II AT1 receptor are not involved in ligand binding but participate in signal transduction, AR.EXT

Abstract

The present project is aimed at understanding the mechanism of action of angiotensin and other peptides (such as bradykinin) through the study of relationships between structure and functions of their receptors, using mutagenesis of isolated residues or from larger segments of the sequence of these proteins. The selection of the position of the residues that will be mutated will be based on three criteria; a) on the analysis of correlated mutation b) on the model of receptor constructed on the basis of the structure of the bacteriorhodopsin and from data which shows bonding modifications caused by mutations of some residues; c) testing the effect of mutations in the residues on the bonding of tachyphylatic and non-tachyphylatic analogues of angiotensin. (AU)