Computationally designed GPCR quaternary structures bias signaling pathway activation

Justine S. Paradis; Xiang Feng; Brigitte Murat; Robert E. Jefferson; Badr Sokrat; Martyna Szpakowska; Mireille Hogue; Nick D. Bergkamp; Franziska M. Heydenreich; Martine J. Smit; Andy Chevigné; Michel Bouvier; Patrick Barth

doi:10.1038/s41467-022-34382-7

Nature Communications (Nov 2022)

Computationally designed GPCR quaternary structures bias signaling pathway activation

Justine S. Paradis,
Xiang Feng,
Brigitte Murat,
Robert E. Jefferson,
Badr Sokrat,
Martyna Szpakowska,
Mireille Hogue,
Nick D. Bergkamp,
Franziska M. Heydenreich,
Martine J. Smit,
Andy Chevigné,
Michel Bouvier,
Patrick Barth

Affiliations

Justine S. Paradis: Department of Biochemistry and Molecular Medicine, Université de Montréal
Xiang Feng: Interfaculty Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne
Brigitte Murat: Department of Biochemistry and Molecular Medicine, Université de Montréal
Robert E. Jefferson: Interfaculty Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne
Badr Sokrat: Department of Biochemistry and Molecular Medicine, Université de Montréal
Martyna Szpakowska: Department of Infection and Immunity, Immuno-Pharmacology and Interactomics, Luxembourg Institute of Health
Mireille Hogue: Institute for Research in Immunology and Cancer (IRIC), Université de Montréal
Nick D. Bergkamp: Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit
Franziska M. Heydenreich: Department of Biochemistry and Molecular Medicine, Université de Montréal
Martine J. Smit: Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit
Andy Chevigné: Department of Infection and Immunity, Immuno-Pharmacology and Interactomics, Luxembourg Institute of Health
Michel Bouvier: Department of Biochemistry and Molecular Medicine, Université de Montréal
Patrick Barth: Interfaculty Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne

DOI: https://doi.org/10.1038/s41467-022-34382-7
Journal volume & issue: Vol. 13, no. 1
pp. 1 – 14

Abstract

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Computational modeling and design of G Protein-Coupled Receptor quaternary structures reveals a signaling bias switch at the receptor dimer interface that selectively controls G protein vs β-arrestin activation.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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