Homologues of human macrophage migration inhibitory factor from a parasitic nematode. Gene cloning, protein activity, and crystal structure.
Zang, Xingxing;
Taylor, Paul;
Wang, Ji Ming;
Meyer, David J;
Scott, Alan L;
Walkinshaw, Malcolm D;
Maizels, Rick M;
(2002)
Homologues of human macrophage migration inhibitory factor from a parasitic nematode. Gene cloning, protein activity, and crystal structure.
The Journal of biological chemistry, 277 (46).
pp. 44261-44267.
ISSN 0021-9258
DOI: https://doi.org/10.1074/jbc.M204655200
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Cytokines are the molecular messengers of the vertebrate immune system, coordinating the local and systemic immune responses to infective organisms. We report here functional and structural data on cytokine-like proteins from a eukaryotic pathogen. Two homologues of the human cytokine macrophage migration inhibitory factor (MIF) have been isolated from the parasitic nematode Brugia malayi. Both molecules (Bm-MIF-1 and Bm-MIF-2) show parallel functions to human MIF. They are chemotactic for human monocytes and activate them to produce IL-8, TNF-alpha, and endogenous MIF. The human and nematode MIF homologues share a tautomerase enzyme activity, which is in each case abolished by the mutation of the N-terminal proline residue. The crystal structure of Bm-MIF-2 at 1.8-A resolution has been determined, revealing a trimeric assembly with an inner pore created by beta-stranded sheets from each subunit. Both biological activity and crystal structure reveal remarkable conservation between a human cytokine and its parasite counterpart despite the considerable phylogenetic divide among these organisms. The strength of the similarity implies that MIF-mediated pathways play an important role in nematode immune evasion strategies.