8DQA

Structure of A. thaliana MIF/D-DT-like protein-3 (MDL3)

8DQA の概要

• エントリーDOI: 10.2210/pdb8dqa/pdb
• 分子名称: LS1-like protein (2 entities in total)
• 機能のキーワード: cytokine
• 由来する生物種: Arabidopsis thaliana (thale cress)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 10912.66

構造登録者

Manjula, R.,Basquin, J.,Lolis, E. (登録日: 2022-07-18, 公開日: 2023-07-26, 最終更新日: 2024-07-03)

主引用文献

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

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: 37988455
DOI: 10.1126/scisignal.adg2621

実験手法

X-RAY DIFFRACTION (2 Å)