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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

12 Issues per year



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

Graciela C. Pignatari1 / Raphael Rozenfeld2 / Emer S. Ferro3 / Laerte Oliveira4 / Antonio C.M. Paiva5 / Lakshmi A. Devi6







Corresponding authors ;

Citation Information: Biological Chemistry. Volume 387, Issue 3, Pages 269–276, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: 10.1515/BC.2006.036, March 2006

Publication History

September 13, 2005
December 16, 2005
Published Online:


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.

Keywords: dimerization; folding; GPCR; maturation; site-directed mutagenesis

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