Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
Board

In the last 30 years, structure/activity studies using peptide analogs yielded information about the structural requisites for angiotensin II (AngII) receptor binding and activation, as well as for other functional phenomena such as receptor desensitization and internalization. More recently, mutagenesis studies revealed the sites in the outer regions of the AT1 receptor involved in AngII binding, as well as the intracellular sites involved in G-protein interaction. Aiming at further understanding the interactions involved in receptor activation and signal transduction we performed sequence alignment analysis on conserved amino acids throughout G protein-coupled receptors and site-directed mutagenesis in the AT1 receptor. Molecular modeling of the ligand-receptor interaction allowed us to propose interactions between the N- and C-terminal regions of AngII and specific receptor residues, which were explored by means of site mutations of the AT1 receptor. Mutational studies also showed that residues in TM-VI are involved in initiating the signal upon receptor binding, and sequence alignment data yielded a model for G-protein activation involving the side-chain of Arg126, located in the distal end of TM-III, and the proximal region of the receptor's C-terminal tail. Based in the available data, a model for the AngII/AT1 interaction and G-protein activation will be discussed.

Back to the top.
Presentation Number SApaiva0625
Keywords: angiotensin, receptor, transduction, signaling, modeling