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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

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


IMPACT FACTOR 2018: 3.014
5-year IMPACT FACTOR: 3.162

CiteScore 2018: 3.09

SCImago Journal Rank (SJR) 2018: 1.482
Source Normalized Impact per Paper (SNIP) 2018: 0.820

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1437-4315
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Volume 393, Issue 11

Issues

β-Barrel scaffolds for the grafting of extracellular loops from G-protein-coupled receptors

Reto Walser
  • Institute of Organic Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
  • Other articles by this author:
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/ Jörg H. Kleinschmidt
  • Department of Biophysics, Institute of Biology, Heinrich-Plett-Str. 40, D-34132 Kassel, Germany
  • Other articles by this author:
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/ Arne Skerra
  • Munich Center for Integrated Protein Science, CIPS-M, and Lehrstuhl für Biologische Chemie, Technische Universität München, D-85350 Freising-Weihenstephan, Germany
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/ Oliver Zerbe
  • Corresponding author
  • Institute of Organic Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
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Published Online: 2012-10-11 | DOI: https://doi.org/10.1515/hsz-2012-0234

Abstract

Owing to the difficulties in production and purification of G-protein-coupled receptors (GPCRs), relatively little structural information is available about this class of receptors. Here we aim at developing small chimeric proteins, displaying the extracellular ligand-binding motifs of a human GPCR, the Y receptor. This allows the study of ligand-receptor interactions in simplified systems. We present comprehensive information on the use of transmembrane (OmpA) and soluble (Blc) β-barrel scaffolds. Whereas Blc appeared to be not fully compatible with our approach, owing to problems with refolding of the hybrid constructs, loop-grafted versions of OmpA delivered encouraging results. Previously, we described a chimeric construct based on OmpA displaying all three extracellular Y1 receptor loops in different topologies and showing moderate affinity to one of the natural ligands. Now, we present detailed data on the interaction of these constructs with several Y receptor ligands along with data on new constructs. Our findings suggest a common binding mode for all ligands, which is mediated through the C-terminal residues of the peptide ligand, supporting the functional validity of these hybrid receptors. The observed binding affinities, however, are well below those observed for the natural receptors, clearly indicating limitations in mimicking the natural systems.

Keywords: membrane proteins; mini-receptor; neurohormones; structural biology; Y receptors

About the article

Corresponding author: Oliver Zerbe, Institute of Organic Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland


Received: 2012-06-17

Accepted: 2012-07-15

Published Online: 2012-10-11

Published in Print: 2012-11-01


Citation Information: , Volume 393, Issue 11, Pages 1341–1355, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2012-0234.

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