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

www.degruyter.com uses cookies, tags, and tracking settings to store information that help give you the very best browsing experience.
To understand more about cookies, tags, and tracking, see our Privacy Statement
I accept all cookies for the De Gruyter Online site

Jump to ContentJump to Main Navigation

Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

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

IMPACT FACTOR increased in 2014: 3.268
Rank 106 out of 289 in category Biochemistry & Molecular Biology in the 2014 Thomson Reuters Journal Citation Report/Science Edition

SCImago Journal Rank (SJR) 2014: 1.596
Source Normalized Impact per Paper (SNIP) 2014: 0.845
Impact per Publication (IPP) 2014: 2.992



30,00 € / $42.00 / £23.00

Get Access to Full Text

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

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

P. Balakumar and G. Jagadeesh
Journal of Molecular Endocrinology, 2014, Volume 53, Number 2, Page R71
Silvana A.A. Correa, Graciela C. Pignatari, Emer S. Ferro, Nelson A.S. Pacheco, Claudio M. Costa-Neto, João B. Pesquero, Laerte Oliveira, Antonio C.M. Paiva, and Suma I. Shimuta
Regulatory Peptides, 2006, Volume 134, Number 2-3, Page 132
Edson L. Santos, Kely de Picoli Souza, Elena Cibrián-Uhalte, Suzana M. Oliveira, Michael Bader, Claudio M. Costa-Neto, Laerte Oliveira, and João B. Pesquero
International Immunopharmacology, 2008, Volume 8, Number 2, Page 282
Raphael Rozenfeld, Achla Gupta, Khatuna Gagnidze, Maribel P Lim, Ivone Gomes, Dinah Lee-Ramos, Natalia Nieto, and Lakshmi A Devi
The EMBO Journal, 2011, Volume 30, Number 12, Page 2350
Renan Paulo Martin, Eliete da Silva Rodrigues, Silvana Aparecida Alves Correa, Suzana Macedo Oliveira, Renato Arruda Mortara, Laerte Oliveira, Clovis Ryuichi Nakaie, and Suma Imura Shimuta
Biological Chemistry, 2010, Volume 391, Number 10

Comments (0)

Please log in or register to comment.