8DQ6
Structure of A. thaliana MIF/D-DT-like protein-1 (MDL1)
Summary for 8DQ6
| Entry DOI | 10.2210/pdb8dq6/pdb |
| Descriptor | MIF/D-DT-like protein-1, CALCIUM ION (3 entities in total) |
| Functional Keywords | cytokine |
| Biological source | Arabidopsis thaliana (thale cress) |
| Total number of polymer chains | 3 |
| Total formula weight | 35326.81 |
| Authors | Manjula, R.,Basquin, J.,Lolis, E. (deposition date: 2022-07-18, release date: 2023-07-26, Last modification date: 2024-07-03) |
| Primary citation | Spiller, L.,Manjula, R.,Leissing, F.,Basquin, J.,Bourilhon, P.,Sinitski, D.,Brandhofer, M.,Levecque, S.,Gerra, S.,Sabelleck, B.,Zhang, L.,Feederle, R.,Flatley, A.,Hoffmann, A.,Panstruga, R.,Bernhagen, J.,Lolis, E. Plant MDL proteins synergize with the cytokine MIF at CXCR2 and CXCR4 receptors in human cells. Sci.Signal., 16:eadg2621-eadg2621, 2023 Cited by PubMed Abstract: 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 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. PubMed: 37988455DOI: 10.1126/scisignal.adg2621 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.56 Å) |
Structure validation
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