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PDBsum entry 2j0h
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Contents |
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* Residue conservation analysis
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PDB id:
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Lectin
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Title:
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L-ficolin complexed to acetyl-choline
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Structure:
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Ficolin-2. Chain: a, b, c, d, e, f. Fragment: c-terminal binding domain, residues 96-313. Synonym: collagen/fibrinogen domain-containing protein 2, ficolin-b, ficolin b, serum lectin p35, ebp-37, hucolin, l-ficolin. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Tissue: plasma. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_cell_line: high five.
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Resolution:
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2.85Å
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R-factor:
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0.213
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R-free:
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0.275
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Authors:
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V.Garlatti,C.Gaboriaud
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Key ref:
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V.Garlatti
et al.
(2007).
Structural insights into the innate immune recognition specificities of L- and H-ficolins.
EMBO J,
26,
623-633.
PubMed id:
DOI:
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Date:
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03-Aug-06
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Release date:
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23-Jan-07
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PROCHECK
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Headers
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References
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Q15485
(FCN2_HUMAN) -
Ficolin-2 from Homo sapiens
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Seq:
Struc:
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313 a.a.
214 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 2 residue positions (black
crosses)
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DOI no:
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EMBO J
26:623-633
(2007)
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PubMed id:
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Structural insights into the innate immune recognition specificities of L- and H-ficolins.
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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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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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Selected figure(s)
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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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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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U.V.Girija,
D.A.Mitchell,
S.Roscher,
and
R.Wallis
(2011).
Carbohydrate recognition and complement activation by rat ficolin-B.
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Eur J Immunol,
41,
214-223.
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Y.Endo,
M.Matsushita,
and
T.Fujita
(2011).
The role of ficolins in the lectin pathway of innate immunity.
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Int J Biochem Cell Biol,
43,
705-712.
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B.Bottazzi,
A.Doni,
C.Garlanda,
and
A.Mantovani
(2010).
An integrated view of humoral innate immunity: pentraxins as a paradigm.
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Annu Rev Immunol,
28,
157-183.
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E.Gout,
V.Garlatti,
D.F.Smith,
M.Lacroix,
C.Dumestre-Pérard,
T.Lunardi,
L.Martin,
J.Y.Cesbron,
G.J.Arlaud,
C.Gaboriaud,
and
N.M.Thielens
(2010).
Carbohydrate recognition properties of human ficolins: glycan array screening reveals the sialic acid binding specificity of M-ficolin.
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J Biol Chem,
285,
6612-6622.
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PDB code:
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E.Hein,
C.Honoré,
M.O.Skjoedt,
L.Munthe-Fog,
T.Hummelshøj,
and
P.Garred
(2010).
Functional analysis of Ficolin-3 mediated complement activation.
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PLoS One,
5,
e15443.
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I.Cestari,
and
M.I.Ramirez
(2010).
Inefficient complement system clearance of Trypanosoma cruzi metacyclic trypomastigotes enables resistant strains to invade eukaryotic cells.
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PLoS One,
5,
e9721.
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M.Hashimoto,
K.Hirota,
H.Yoshitomi,
S.Maeda,
S.Teradaira,
S.Akizuki,
P.Prieto-Martin,
T.Nomura,
N.Sakaguchi,
J.Köhl,
B.Heyman,
M.Takahashi,
T.Fujita,
T.Mimori,
and
S.Sakaguchi
(2010).
Complement drives Th17 cell differentiation and triggers autoimmune arthritis.
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J Exp Med,
207,
1135-1143.
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T.Thomsen,
J.B.Moeller,
A.Schlosser,
G.L.Sorensen,
S.K.Moestrup,
N.Palaniyar,
R.Wallis,
J.Mollenhauer,
and
U.Holmskov
(2010).
The recognition unit of FIBCD1 organizes into a noncovalently linked tetrameric structure and uses a hydrophobic funnel (S1) for acetyl group recognition.
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J Biol Chem,
285,
1229-1238.
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I.Söderhäll,
C.Wu,
M.Novotny,
B.L.Lee,
and
K.Söderhäll
(2009).
A Novel Protein Acts as a Negative Regulator of Prophenoloxidase Activation and Melanization in the Freshwater Crayfish Pacifastacus leniusculus.
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J Biol Chem,
284,
6301-6310.
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J.Zhang,
J.Koh,
J.Lu,
S.Thiel,
B.S.Leong,
S.Sethi,
C.Y.He,
B.Ho,
and
J.L.Ding
(2009).
Local inflammation induces complement crosstalk which amplifies the antimicrobial response.
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PLoS Pathog,
5,
e1000282.
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Y.J.Ma,
A.Doni,
T.Hummelshøj,
C.Honoré,
A.Bastone,
A.Mantovani,
N.M.Thielens,
and
P.Garred
(2009).
Synergy between ficolin-2 and pentraxin 3 boosts innate immune recognition and complement deposition.
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J Biol Chem,
284,
28263-28275.
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M.K.Pangburn,
V.P.Ferreira,
and
C.Cortes
(2008).
Discrimination between host and pathogens by the complement system.
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Vaccine,
26,
I15-I21.
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M.Tanio,
S.Kondo,
S.Sugio,
and
T.Kohno
(2008).
Trimeric structure and conformational equilibrium of M-ficolin fibrinogen-like domain.
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J Synchrotron Radiat,
15,
243-245.
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Y.Aoyagi,
E.E.Adderson,
C.E.Rubens,
J.F.Bohnsack,
J.G.Min,
M.Matsushita,
T.Fujita,
Y.Okuwaki,
and
S.Takahashi
(2008).
L-ficolin/mannose-binding lectin-associated serine protease complexes bind to group B streptococci primarily through N-acetylneuraminic acid of capsular polysaccharide and activate the complement pathway.
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Infect Immun,
76,
179-188.
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C.Honoré,
T.Hummelshoj,
B.E.Hansen,
H.O.Madsen,
P.Eggleton,
and
P.Garred
(2007).
The innate immune component ficolin 3 (Hakata antigen) mediates the clearance of late apoptotic cells.
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Arthritis Rheum,
56,
1598-1607.
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U.V.Girija,
A.W.Dodds,
S.Roscher,
K.B.Reid,
and
R.Wallis
(2007).
Localization and characterization of the mannose-binding lectin (MBL)-associated-serine protease-2 binding site in rat ficolin-A: equivalent binding sites within the collagenous domains of MBLs and ficolins.
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J Immunol,
179,
455-462.
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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
