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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

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

12 Issues per year


IMPACT FACTOR 2016: 3.273

CiteScore 2016: 3.01

SCImago Journal Rank (SJR) 2016: 1.679
Source Normalized Impact per Paper (SNIP) 2016: 0.800

Online
ISSN
1437-4315
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Volume 387, Issue 3 (Mar 2006)

Issues

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

Graciela C. Pignatari / Raphael Rozenfeld
  • Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Emer S. Ferro
  • Department of Cell Biology and Development, University of São Paulo, São Paulo 05508-900, Brazil
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Laerte Oliveira / Antonio C.M. Paiva / Lakshmi A. Devi
  • Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2006-03-17 | DOI: https://doi.org/10.1515/BC.2006.036

Abstract

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

About the article

Corresponding authors ;


Received: September 13, 2005

Accepted: December 16, 2005

Published Online: 2006-03-17

Published in Print: 2006-03-01


Citation Information: Biological Chemistry, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2006.036.

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