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Plant MDL proteins synergize with the cytokine MIF at CXCR2 and CXCR4 receptors in human cells.
Sci. Signal. 16:eadg2621 (2023)
Mammalian macrophage migration inhibitory factor (MIF) and its paralog, D-dopachrome tautomerase, are multifunctional inflammatory cytokines. Plants have orthologous MIF and D-dopachrome tautomerase-like (MDL) proteins that mimic some of the effects of MIF on immune cells in vitro. We explored the structural and functional similarities between the three Arabidopsis thaliana MDLs and MIF. X-ray crystallography of the MDLs revealed high structural similarity between MDL and MIF homotrimers and suggested a potential explanation for the lack of tautomerase activity in the MDLs. MDL1 and MDL2 interacted with each other and with MIF in vitro, in yeast, and in plant leaves and formed hetero-oligomeric complexes with MIF in vitro. The MDLs stimulated signaling through the MIF receptors CXCR2 or CXCR4 and enhanced the responses to MIF in a yeast reporter system, in human neutrophils, and in human lung epithelial cells. Pharmacological inhibitors that disrupted MIF activity or prevented the formation of MIF-MDL hetero-oligomers blocked the observed synergism. These findings demonstrate that MDLs can enhance cellular responses to MIF, which may have functional implications in tissues exposed to MDLs from the diet or environment.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Migration Inhibitory Factor; Oligomerization State; Crystal-structure; Active-site; Activation; Identification; Discovery; Chemokine; Survival; Features
ISSN (print) / ISBN
1945-0877
e-ISSN
1937-9145
Journal
Science Signaling
Quellenangaben
Volume: 16,
Issue: 812,
Article Number: eadg2621
Publisher
American Association for the Advancement of Science (AAAS)
Publishing Place
1200 New York Ave, Nw, Washington, Dc 20005 Usa
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
CF Monoclonal Antibodies (CF-MAB)
Grants
LMUexc-KTF program of LMU Munich
Studienstiftungdes Deutschen Volkes
Open Philanthropy
DFG under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy)
DFG
German Research Foundation)-Agence Nationale Recherche (ANR)
Deutsche Forschungsgemeinschaft (DFG
Studienstiftungdes Deutschen Volkes
Open Philanthropy
DFG under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy)
DFG
German Research Foundation)-Agence Nationale Recherche (ANR)
Deutsche Forschungsgemeinschaft (DFG