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PDBsum entry 2j0h
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References listed in PDB file
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Key reference
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Title
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Structural insights into the innate immune recognition specificities of l- And h-Ficolins.
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Authors
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V.Garlatti,
N.Belloy,
L.Martin,
M.Lacroix,
M.Matsushita,
Y.Endo,
T.Fujita,
J.C.Fontecilla-Camps,
G.J.Arlaud,
N.M.Thielens,
C.Gaboriaud.
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Ref.
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EMBO J, 2007,
26,
623-633.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
perfect match.
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Abstract
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Innate immunity relies critically upon the ability of a few pattern recognition
molecules to sense molecular markers on pathogens, but little is known about
these interactions at the atomic level. Human L- and H-ficolins are soluble
oligomeric defence proteins with lectin-like activity, assembled from collagen
fibers prolonged by fibrinogen-like recognition domains. The X-ray structures of
their trimeric recognition domains, alone and in complex with various ligands,
have been solved to resolutions up to 1.95 and 1.7 A, respectively. Both domains
have three-lobed structures with clefts separating the distal parts of the
protomers. Ca(2+) ions are found at sites homologous to those described for
tachylectin 5A (TL5A), an invertebrate lectin. Outer binding sites (S1)
homologous to the GlcNAc-binding pocket of TL5A are present in the ficolins but
show different structures and specificities. In L-ficolin, three additional
binding sites (S2-S4) surround the cleft. Together, they define an unpredicted
continuous recognition surface able to sense various acetylated and neutral
carbohydrate markers in the context of extended polysaccharides such as
1,3-beta-D-glucan, as found on microbial or apoptotic surfaces.
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Figure 1.
Figure 1 Homotrimeric structure of the recognition domains of
human L- and H-ficolins and location of their binding site(s).
(A, B) L-ficolin structure seen from the target binding surface
(bottom view) and on a perpendicular side view. (C, D)
Corresponding bottom and side views of the H-ficolin structure.
The side chains of the binding site residues are displayed as
ball and sticks and colored green (S1), red (S2), black (S3),
and orange (S4). To enhance clarity of the side view, only one
of each representative binding sites is shown on the L-ficolin
trimer. N and C indicate the N- and C-terminal ends of each
protomer. Ca^2+ ions are represented as golden spheres. Figure
generated using MOLSCRIPT (Kraulis, 1991).
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Figure 3.
Figure 3 Comparative views of the S1 binding site in H-ficolin,
L-ficolin, and TL5A. The side chains of the residues defining S1
are colored green and the ligands are displayed in yellow. (A)
D-Fucose bound to H-ficolin. (B) GlcNAc bound to TL5A. (C) The
terminal mannose of the oligosaccharide chain from a neighboring
molecule positioned in site S1 of L-ficolin. On the left, the
two proximal GlcNAc residues of the chain interacting on the
edge of the binding site.
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(2007,
26,
623-633)
copyright 2007.
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