GPR180 is a new member of the Golgi-dynamics domain seven-transmembrane helix protein family

Abstract GOLD domain seven-transmembrane helix (GOST) proteins form a new protein family involved in trafficking of membrane-associated cargo. They share a characteristic extracellular/luminal Golgi-dynamics (GOLD) domain, possibly responsible for ligand recognition. Based on structural homology, GP...

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Main Authors: Sarah-Ana Mitrovic, Chamalee Demalgiriya-Gamage, Lisa-Maria Winter, Tobias Kiechle, Rebecca Ebenhoch, Heike Neubauer, Birgit Stierstorfer, Lee Frego, Christian Wolfrum, Sophia Reindl, Herbert Nar
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-024-07260-9
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author Sarah-Ana Mitrovic
Chamalee Demalgiriya-Gamage
Lisa-Maria Winter
Tobias Kiechle
Rebecca Ebenhoch
Heike Neubauer
Birgit Stierstorfer
Lee Frego
Christian Wolfrum
Sophia Reindl
Herbert Nar
author_facet Sarah-Ana Mitrovic
Chamalee Demalgiriya-Gamage
Lisa-Maria Winter
Tobias Kiechle
Rebecca Ebenhoch
Heike Neubauer
Birgit Stierstorfer
Lee Frego
Christian Wolfrum
Sophia Reindl
Herbert Nar
author_sort Sarah-Ana Mitrovic
collection DOAJ
description Abstract GOLD domain seven-transmembrane helix (GOST) proteins form a new protein family involved in trafficking of membrane-associated cargo. They share a characteristic extracellular/luminal Golgi-dynamics (GOLD) domain, possibly responsible for ligand recognition. Based on structural homology, GPR180 is a new member of this protein family, but little is known about the cellular role of GPR180. Here we show the X-ray structure of the N-terminal domain of GPR180 (1.9 Å) and can confirm the homology to GOLD domains. Using cellular imaging we show the localization of GPR180 in intracellular vesicular structures implying its exposure to acidic pH environments. With Hydrogen/Deuterium Exchange-Mass Spectrometry (HDX-MS) we identify pH-dependent conformational changes, which can be mapped to a putative ligand binding site in the transmembrane region. The results reveal GPR180’s role in intracellular vesicles and offer insights into the pH-dependent function of this conserved GOST protein.
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spelling doaj-art-88c3854804c44e81b7ebbe77ff86b7f82025-08-20T02:38:35ZengNature PortfolioCommunications Biology2399-36422024-11-017111410.1038/s42003-024-07260-9GPR180 is a new member of the Golgi-dynamics domain seven-transmembrane helix protein familySarah-Ana Mitrovic0Chamalee Demalgiriya-Gamage1Lisa-Maria Winter2Tobias Kiechle3Rebecca Ebenhoch4Heike Neubauer5Birgit Stierstorfer6Lee Frego7Christian Wolfrum8Sophia Reindl9Herbert Nar10Boehringer Ingelheim Pharma GmbH & Co. KGBoehringer IngelheimBoehringer Ingelheim Pharma GmbH & Co. KGBoehringer Ingelheim Pharma GmbH & Co. KGBoehringer Ingelheim Pharma GmbH & Co. KGBoehringer Ingelheim Pharma GmbH & Co. KGBoehringer Ingelheim Pharma GmbH & Co. KGBoehringer IngelheimDepartment of Health Sciences and Technology, ETH ZürichBoehringer Ingelheim Pharma GmbH & Co. KGBoehringer Ingelheim Pharma GmbH & Co. KGAbstract GOLD domain seven-transmembrane helix (GOST) proteins form a new protein family involved in trafficking of membrane-associated cargo. They share a characteristic extracellular/luminal Golgi-dynamics (GOLD) domain, possibly responsible for ligand recognition. Based on structural homology, GPR180 is a new member of this protein family, but little is known about the cellular role of GPR180. Here we show the X-ray structure of the N-terminal domain of GPR180 (1.9 Å) and can confirm the homology to GOLD domains. Using cellular imaging we show the localization of GPR180 in intracellular vesicular structures implying its exposure to acidic pH environments. With Hydrogen/Deuterium Exchange-Mass Spectrometry (HDX-MS) we identify pH-dependent conformational changes, which can be mapped to a putative ligand binding site in the transmembrane region. The results reveal GPR180’s role in intracellular vesicles and offer insights into the pH-dependent function of this conserved GOST protein.https://doi.org/10.1038/s42003-024-07260-9
spellingShingle Sarah-Ana Mitrovic
Chamalee Demalgiriya-Gamage
Lisa-Maria Winter
Tobias Kiechle
Rebecca Ebenhoch
Heike Neubauer
Birgit Stierstorfer
Lee Frego
Christian Wolfrum
Sophia Reindl
Herbert Nar
GPR180 is a new member of the Golgi-dynamics domain seven-transmembrane helix protein family
Communications Biology
title GPR180 is a new member of the Golgi-dynamics domain seven-transmembrane helix protein family
title_full GPR180 is a new member of the Golgi-dynamics domain seven-transmembrane helix protein family
title_fullStr GPR180 is a new member of the Golgi-dynamics domain seven-transmembrane helix protein family
title_full_unstemmed GPR180 is a new member of the Golgi-dynamics domain seven-transmembrane helix protein family
title_short GPR180 is a new member of the Golgi-dynamics domain seven-transmembrane helix protein family
title_sort gpr180 is a new member of the golgi dynamics domain seven transmembrane helix protein family
url https://doi.org/10.1038/s42003-024-07260-9
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