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PDBsum entry 3b64
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References listed in PDB file
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Key reference
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Title
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A leishmania ortholog of macrophage migration inhibitory factor modulates host macrophage responses.
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Authors
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D.Kamir,
S.Zierow,
L.Leng,
Y.Cho,
Y.Diaz,
J.Griffith,
C.Mcdonald,
M.Merk,
R.A.Mitchell,
J.Trent,
Y.Chen,
Y.K.Kwong,
H.Xiong,
J.Vermeire,
M.Cappello,
D.Mcmahon-Pratt,
J.Walker,
J.Bernhagen,
E.Lolis,
R.Bucala.
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Ref.
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J Immunol, 2008,
180,
8250-8261.
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PubMed id
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Abstract
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Parasitic organisms have evolved specialized strategies to evade immune defense
mechanisms. We describe herein an ortholog of the cytokine, macrophage migration
inhibitory factor (MIF), which is produced by the obligate intracellular
parasite, Leishmania major. The Leishmania MIF protein, Lm1740MIF, shows
significant structural homology with human MIF as revealed by a high-resolution
x-ray crystal structure (1.03 A). Differences between the two proteins in the
N-terminal tautomerization site are evident, and we provide evidence for the
selective, species-specific inhibition of MIF by small-molecule antagonists that
target this site. Lm1740MIF shows significant binding interaction with the MIF
receptor, CD74 (K(d) = 2.9 x 10(-8) M). Like its mammalian counterpart,
Lm1740MIF induces ERK1/2 MAP kinase activation in a CD74-dependent manner and
inhibits the activation-induced apoptosis of macrophages. The ability of
Lm1740MIF to inhibit apoptosis may facilitate the persistence of Leishmania
within the macrophage and contribute to its evasion from immune destruction.
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