Plant MDL proteins synergize with the cytokine MIF at CXCR2 and CXCR4 receptors in human cells.

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.

Characterization of Plasmodium falciparum macrophage migration inhibitory factor homologue and its cysteine deficient mutants.

Plasmodium falciparum macrophage migration inhibitory factor (PfMIF) is a homologue of the multifunctional human host cytokine MIF (HsMIF). Upon schizont rupture it is released into the human blood stream where it acts as a virulence factor, modulating the host immune system. Whereas for HsMIF a tautomerase, an oxidoreductase, and a nuclease activity have been identified, the latter has not yet been studied for PfMIF.

Designed CXCR4 mimic acts as a soluble chemokine receptor that blocks atherogenic inflammation by agonist-specific targeting.

Targeting a specific chemokine/receptor axis in atherosclerosis remains challenging. Soluble receptor-based strategies are not established for chemokine receptors due to their discontinuous architecture. Macrophage migration-inhibitory factor (MIF) is an atypical chemokine that promotes atherosclerosis through CXC-motif chemokine receptor-4 (CXCR4).

Identification of an Arg-Leu-Arg tripeptide that contributes to the binding interface between the cytokine MIF and the chemokine receptor CXCR4.

MIF is a chemokine-like cytokine that plays a role in the pathogenesis of inflammatory and cardiovascular disorders. It binds to the chemokine-receptors CXCR2/CXCR4 to trigger atherogenic leukocyte migration albeit lacking canonical chemokine structures. We recently characterized an N-like-loop and the Pro-2-residue of MIF as critical molecular determinants of the CXCR4/MIF binding-site and identified allosteric agonism as a mechanism that distinguishes CXCR4-binding to MIF from that to the cognate ligand CXCL12.