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PDBsum entry 3b64
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* Residue conservation analysis
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J Immunol
180:8250-8261
(2008)
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PubMed id:
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A Leishmania ortholog of macrophage migration inhibitory factor modulates host macrophage responses.
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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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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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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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E.Mougneau,
F.Bihl,
and
N.Glaichenhaus
(2011).
Cell biology and immunology of Leishmania.
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Immunol Rev,
240,
286-296.
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F.Li,
S.Huang,
L.Wang,
J.Yang,
H.Zhang,
L.Qiu,
L.Li,
and
L.Song
(2011).
A macrophage migration inhibitory factor like gene from scallop Chlamys farreri: Involvement in immune response and wound healing.
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Dev Comp Immunol,
35,
62-71.
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R.L.Rich,
and
D.G.Myszka
(2010).
Grading the commercial optical biosensor literature-Class of 2008: 'The Mighty Binders'.
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J Mol Recognit,
23,
1.
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A.M.Filip,
J.Klug,
S.Cayli,
S.Fröhlich,
T.Henke,
P.Lacher,
R.Eickhoff,
P.Bulau,
M.Linder,
C.Carlsson-Skwirut,
L.Leng,
R.Bucala,
S.Kraemer,
J.Bernhagen,
and
A.Meinhardt
(2009).
Ribosomal protein S19 interacts with macrophage migration inhibitory factor and attenuates its pro-inflammatory function.
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J Biol Chem,
284,
7977-7985.
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L.Prieto-Lafuente,
W.F.Gregory,
J.E.Allen,
and
R.M.Maizels
(2009).
MIF homologues from a filarial nematode parasite synergize with IL-4 to induce alternative activation of host macrophages.
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J Leukoc Biol,
85,
844-854.
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S.E.Dobson,
K.D.Augustijn,
J.A.Brannigan,
C.Schnick,
C.J.Janse,
E.J.Dodson,
A.P.Waters,
and
A.J.Wilkinson
(2009).
The crystal structures of macrophage migration inhibitory factor from Plasmodium falciparum and Plasmodium berghei.
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Protein Sci,
18,
2578-2591.
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PDB codes:
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V.Schwartz,
H.Lue,
S.Kraemer,
J.Korbiel,
R.Krohn,
K.Ohl,
R.Bucala,
C.Weber,
and
J.Bernhagen
(2009).
A functional heteromeric MIF receptor formed by CD74 and CXCR4.
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FEBS Lett,
583,
2749-2757.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
