Evolutionary analyses reveal immune cell receptor GPR84 as a conserved receptor for bacteria-derived molecules

Summary: The G protein-coupled receptor 84 (GPR84) is found in immune cells and its expression is increased under inflammatory conditions. Activation of GPR84 by medium-chain fatty acids results in pro-inflammatory responses. Here, we screened available vertebrate genome data and found that GPR84 is...

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Main Authors: Amadeus Samuel Schulze, Gunnar Kleinau, Rosanna Krakowsky, David Rochmann, Ranajit Das, Catherine L. Worth, Petra Krumbholz, Patrick Scheerer, Claudia Stäubert
Format: Article
Language:English
Published: Elsevier 2022-10-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004222013591
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author Amadeus Samuel Schulze
Gunnar Kleinau
Rosanna Krakowsky
David Rochmann
Ranajit Das
Catherine L. Worth
Petra Krumbholz
Patrick Scheerer
Claudia Stäubert
author_facet Amadeus Samuel Schulze
Gunnar Kleinau
Rosanna Krakowsky
David Rochmann
Ranajit Das
Catherine L. Worth
Petra Krumbholz
Patrick Scheerer
Claudia Stäubert
author_sort Amadeus Samuel Schulze
collection DOAJ
description Summary: The G protein-coupled receptor 84 (GPR84) is found in immune cells and its expression is increased under inflammatory conditions. Activation of GPR84 by medium-chain fatty acids results in pro-inflammatory responses. Here, we screened available vertebrate genome data and found that GPR84 is present in vertebrates for more than 500 million years but absent in birds and a pseudogene in bats. Cloning and functional characterization of several mammalian GPR84 orthologs in combination with evolutionary and model-based structural analyses revealed evidence for positive selection of bear GPR84 orthologs. Naturally occurring human GPR84 variants are most frequent in Asian populations causing a loss of function. Further, we identified cis- and trans-2-decenoic acid, both known to mediate bacterial communication, as evolutionary highly conserved ligands. Our integrated set of approaches contributes to a comprehensive understanding of GPR84 in terms of evolutionary and structural aspects, highlighting GPR84 as a conserved immune cell receptor for bacteria-derived molecules.
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spelling doaj.art-9327fa6e680f4359b0498678101c4e362022-12-22T01:48:04ZengElsevieriScience2589-00422022-10-012510105087Evolutionary analyses reveal immune cell receptor GPR84 as a conserved receptor for bacteria-derived moleculesAmadeus Samuel Schulze0Gunnar Kleinau1Rosanna Krakowsky2David Rochmann3Ranajit Das4Catherine L. Worth5Petra Krumbholz6Patrick Scheerer7Claudia Stäubert8Rudolf Schönheimer Institute of Biochemistry, Faculty of Medicine, Leipzig University, Johannisallee 30, 04103 Leipzig, GermanyCharité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Physics and Biophysics, Group Protein X-ray Crystallography and Signal Transduction, Charitéplatz 1, 10117 Berlin, GermanyRudolf Schönheimer Institute of Biochemistry, Faculty of Medicine, Leipzig University, Johannisallee 30, 04103 Leipzig, GermanyRudolf Schönheimer Institute of Biochemistry, Faculty of Medicine, Leipzig University, Johannisallee 30, 04103 Leipzig, GermanyYenepoya Research Centre, Yenepoya University, Mangalore, Karnataka, IndiaIndependent Data Lab UG, Frauenmantelanger 31, 80937 Munich, GermanyRudolf Schönheimer Institute of Biochemistry, Faculty of Medicine, Leipzig University, Johannisallee 30, 04103 Leipzig, GermanyCharité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Physics and Biophysics, Group Protein X-ray Crystallography and Signal Transduction, Charitéplatz 1, 10117 Berlin, GermanyRudolf Schönheimer Institute of Biochemistry, Faculty of Medicine, Leipzig University, Johannisallee 30, 04103 Leipzig, Germany; Corresponding authorSummary: The G protein-coupled receptor 84 (GPR84) is found in immune cells and its expression is increased under inflammatory conditions. Activation of GPR84 by medium-chain fatty acids results in pro-inflammatory responses. Here, we screened available vertebrate genome data and found that GPR84 is present in vertebrates for more than 500 million years but absent in birds and a pseudogene in bats. Cloning and functional characterization of several mammalian GPR84 orthologs in combination with evolutionary and model-based structural analyses revealed evidence for positive selection of bear GPR84 orthologs. Naturally occurring human GPR84 variants are most frequent in Asian populations causing a loss of function. Further, we identified cis- and trans-2-decenoic acid, both known to mediate bacterial communication, as evolutionary highly conserved ligands. Our integrated set of approaches contributes to a comprehensive understanding of GPR84 in terms of evolutionary and structural aspects, highlighting GPR84 as a conserved immune cell receptor for bacteria-derived molecules.http://www.sciencedirect.com/science/article/pii/S2589004222013591Biological sciencesEvolutionary biologyEvolutionary processes
spellingShingle Amadeus Samuel Schulze
Gunnar Kleinau
Rosanna Krakowsky
David Rochmann
Ranajit Das
Catherine L. Worth
Petra Krumbholz
Patrick Scheerer
Claudia Stäubert
Evolutionary analyses reveal immune cell receptor GPR84 as a conserved receptor for bacteria-derived molecules
iScience
Biological sciences
Evolutionary biology
Evolutionary processes
title Evolutionary analyses reveal immune cell receptor GPR84 as a conserved receptor for bacteria-derived molecules
title_full Evolutionary analyses reveal immune cell receptor GPR84 as a conserved receptor for bacteria-derived molecules
title_fullStr Evolutionary analyses reveal immune cell receptor GPR84 as a conserved receptor for bacteria-derived molecules
title_full_unstemmed Evolutionary analyses reveal immune cell receptor GPR84 as a conserved receptor for bacteria-derived molecules
title_short Evolutionary analyses reveal immune cell receptor GPR84 as a conserved receptor for bacteria-derived molecules
title_sort evolutionary analyses reveal immune cell receptor gpr84 as a conserved receptor for bacteria derived molecules
topic Biological sciences
Evolutionary biology
Evolutionary processes
url http://www.sciencedirect.com/science/article/pii/S2589004222013591
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