TY - JOUR
T1 - Homologues of human macrophage migration inhibitory factor from a parasitic nematode
T2 - Gene cloning, protein activity, and crystal structure
AU - Zang, Xingxing
AU - Taylor, Paul
AU - Wang, Ji Ming
AU - Meyer, David J.
AU - Scott, Alan L.
AU - Walkinshaw, Malcolm D.
AU - Maizels, Rick M.
PY - 2002/11/15
Y1 - 2002/11/15
N2 - 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 cytokinelike 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-α, 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-Å resolution has been determined, revealing a trimeric assembly with an inner pore created by β-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.
AB - 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 cytokinelike 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-α, 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-Å resolution has been determined, revealing a trimeric assembly with an inner pore created by β-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.
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U2 - 10.1074/jbc.M204655200
DO - 10.1074/jbc.M204655200
M3 - Article
C2 - 12221083
AN - SCOPUS:0347928886
SN - 0021-9258
VL - 277
SP - 44261
EP - 44267
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 46
ER -