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PDBsum entry 2os5
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* Residue conservation analysis
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DOI no:
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J Biol Chem
282:23447-23456
(2007)
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PubMed id:
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Structural and functional characterization of a secreted hookworm Macrophage Migration Inhibitory Factor (MIF) that interacts with the human MIF receptor CD74.
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Y.Cho,
B.F.Jones,
J.J.Vermeire,
L.Leng,
L.DiFedele,
L.M.Harrison,
H.Xiong,
Y.K.Kwong,
Y.Chen,
R.Bucala,
E.Lolis,
M.Cappello.
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ABSTRACT
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Hookworms, parasitic nematodes that infect nearly one billion people worldwide,
are a major cause of anemia and malnutrition. We hypothesize that hookworms
actively manipulate the host immune response through the production of specific
molecules designed to facilitate infection by larval stages and adult worm
survival within the intestine. A full-length cDNA encoding a secreted orthologue
of the human cytokine, Macrophage Migration Inhibitory Factor (MIF) has been
cloned from the hookworm Ancylostoma ceylanicum. Elucidation of the
three-dimensional crystal structure of recombinant AceMIF (rAceMIF) revealed an
overall structural homology with significant differences in the tautomerase
sites of the human and hookworm proteins. The relative bioactivities of human
and hookworm MIF proteins were compared using in vitro assays of tautomerase
activity, macrophage migration, and binding to MIF receptor CD74. The activity
of rAceMIF was not inhibited by the ligand ISO-1, which was previously
determined to be an inhibitor of the catalytic site of human MIF. These data
define unique immunological, structural, and functional characteristics of
AceMIF, thereby establishing the potential for selectively inhibiting the
hookworm cytokine as a means of reducing parasite survival and disease
pathogenesis.
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Selected figure(s)
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Figure 3.
FIGURE 3. Topological comparison of AceMIF and hMIF. A,
backbone ribbon diagrams of AceMIF and hMIF. Secondary
structural elements are represented in red (  -helix), yellow (  -strand),
and green (random coil). B, trimers of the two MIFs are
superimposed. Human MIF is represented in yellow and AceMIF in
red. The approximate location of the active site is between two
subunits and indicated by the designation Pro1.
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Figure 5.
FIGURE 5. Comparative views of the active sites of hMIF and
AceMIF. A, view into the cavity of the active sites of AceMIF
and hMIF. The figure shows the substrate HPP bound in the active
site of hMIF (50), which is displayed in stick representation.
B, superposition of the active sites of AceMIF and hMIF, with
HPP bound to hMIF. Residues within hydrogen-bonding distance to
HPP are colored in red (AceMIF) or yellow (hMIF). Residue codes
correspond to AceMIF. Residues in parentheses correspond to
hMIF. Two adjacent protomers (colored in cyan and green) in the
trimer form the active site, and there are three active sites in
each trimer. C, hydrogen bonds and hydrophobic interactions
between HPP and interacting residues in a model of AceMIF:HPP
and the crystal structure of hMIF:HPP (50), respectively, are
shown. The residues involved in hydrophobic interactions with
HPP are drawn as a spiked hemisphere. Distances for hydrogen
bonds are in green dashed lines with their distance in Angstrom
units.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2007,
282,
23447-23456)
copyright 2007.
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Figures were
selected
by an automated process.
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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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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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K.Kucera,
L.M.Harrison,
M.Cappello,
and
Y.Modis
(2011).
Ancylostoma ceylanicum excretory-secretory protein 2 adopts a netrin-like fold and defines a novel family of nematode proteins.
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J Mol Biol,
408,
9.
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PDB code:
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M.K.Cho,
C.H.Lee,
and
H.S.Yu
(2011).
Amelioration of intestinal colitis by macrophage migration inhibitory factor isolated from intestinal parasites through toll-like receptor 2.
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Parasite Immunol,
33,
265-275.
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R.Bungiro,
and
M.Cappello
(2011).
Twenty-first century progress toward the global control of human hookworm infection.
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Curr Infect Dis Rep,
13,
210-217.
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A.Baeza Garcia,
R.J.Pierce,
B.Gourbal,
E.Werkmeister,
D.Colinet,
J.M.Reichhart,
C.Dissous,
and
C.Coustau
(2010).
Involvement of the cytokine MIF in the snail host immune response to the parasite Schistosoma mansoni.
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PLoS Pathog,
6,
0.
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T.D.Schoep,
A.Fulurija,
F.Good,
W.Lu,
R.P.Himbeck,
C.Schwan,
S.S.Choi,
D.E.Berg,
P.R.Mittl,
M.Benghezal,
and
B.J.Marshall
(2010).
Surface properties of Helicobacter pylori urease complex are essential for persistence.
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PLoS One,
5,
e15042.
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Y.Cho,
G.V.Crichlow,
J.J.Vermeire,
L.Leng,
X.Du,
M.E.Hodsdon,
R.Bucala,
M.Cappello,
M.Gross,
F.Gaeta,
K.Johnson,
and
E.J.Lolis
(2010).
Allosteric inhibition of macrophage migration inhibitory factor revealed by ibudilast.
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Proc Natl Acad Sci U S A,
107,
11313-11318.
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PDB codes:
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B.L.Barrilleaux,
D.G.Phinney,
B.W.Fischer-Valuck,
K.C.Russell,
G.Wang,
D.J.Prockop,
and
K.C.O'Connor
(2009).
Small-molecule antagonist of macrophage migration inhibitory factor enhances migratory response of mesenchymal stem cells to bronchial epithelial cells.
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Tissue Eng Part A,
15,
2335-2346.
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J.P.Hewitson,
J.R.Grainger,
and
R.M.Maizels
(2009).
Helminth immunoregulation: the role of parasite secreted proteins in modulating host immunity.
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Mol Biochem Parasitol,
167,
1.
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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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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,
and
R.Bucala
(2008).
A Leishmania ortholog of macrophage migration inhibitory factor modulates host macrophage responses.
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J Immunol,
180,
8250-8261.
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PDB code:
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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
code is
shown on the right.
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Links
