Evidence map›Paper›PMID 36824923›Full record

ArticleResearch square2023

Pro-phagocytic function and structural basis of GPR84 signaling.

Xuan Zhang, Yujing Wang, Shreyas Supekar, Xu Cao, Jingkai Zhou, Jessica Dang, Siqi Chen, Laura Jenkins, Sara Marsango, Xiu Li and 6 more

Open access · greenAbstract readPreprint
In one paragraph

Article in Research square, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 3 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 5 institutions in 4 countries.

Xuan ZhangDivision of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Yujing WangDivision of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Shreyas SupekarBioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), 138671, Singapore.ORCID 0000-0003-3353-4327
Xu CaoDepartment of Immuno-Oncology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
Jingkai ZhouDepartment of Immuno-Oncology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
Jessica DangDepartment of Immuno-Oncology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
Siqi ChenDepartment of Immuno-Oncology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
Laura JenkinsCentre for Translational Pharmacology, School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K.
Sara MarsangoCentre for Translational Pharmacology, School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K.
Xiu LiDivision of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Guibing LiuDivision of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Graeme MilliganCentre for Translational Pharmacology, School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K.ORCID 0000-0002-6946-3519
Mingye FengDepartment of Immuno-Oncology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
Hao FanBioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), 138671, Singapore.ORCID 0000-0003-0199-9752
Weimin GongDivision of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Cheng ZhangDepartment of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.ORCID 0000-0001-9042-4007
City of Hope · USUniversity of Science and Technology of China · CNUniversity of Glasgow · GBAgency for Science, Technology and Research · SGUniversity of Pittsburgh · US

Funding

Structure, pharmacology and signaling of G protein-coupled receptors (GPCRs) in inflammationR35GM128641 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHENG ZHANG · 2018 to 2026
$3.5M
NIGMS NIH HHS R35 GM128641
6 · The paper itself

Abstract

GPR84 is a unique orphan G protein-coupled receptor (GPCR) that can be activated by endogenous medium-chain fatty acids (MCFAs). The signaling of GPR84 is largely pro-inflammatory, which can augment inflammatory response, and GPR84 also functions as a pro-phagocytic receptor to enhance the phagocytic activities of macrophages. In this study, we first showed that the activation of GPR84 by the synthetic agonist 6-OAU could synergize with the blockade of CD47 on cancer cells to induce phagocytosis of cancer cells by macrophages. Then, we determined a high-resolution structure of the GPR84-Gi signaling complex with 6-OAU. This structure revealed a completely occluded binding pocket for 6-OAU, the molecular basis of receptor activation involving non-conserved structural motifs of GPR84, and an unusual Gi-coupling interface. Together with computational docking and simulations studies, our structure also suggested the mechanism for the high selectivity of GPR84 for MCFAs and the potential routes of ligand binding and dissociation. Our results provide a framework for understanding GPR84 signaling and developing new drugs targeting GPR84.

Identifiers

PMID36824923
PMCPMC9949259
OpenAlexW4320893582

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.