 |
PDBsum entry 2d39
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Immune system
|
PDB id
|
|
|
|
2d39
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Trivalent recognition unit of innate immunity system: crystal structure of trimeric human m-Ficolin fibrinogen-Like domain.
|
|
|
Authors
|
|
M.Tanio,
S.Kondo,
S.Sugio,
T.Kohno.
|
|
|
Ref.
|
|
J Biol Chem, 2007,
282,
3889-3895.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Ficolins are a kind of pathogen-recognition molecule in the innate immune
systems. To investigate the discrimination mechanism between self and non-self
by ficolins, we determined the crystal structure of the human M-ficolin
fibrinogen-like domain (FD1), which is the ligand-binding domain, at 1.9A
resolution. Although the FD1 monomer shares a common fold with the fibrinogen
gamma fragment and tachylectin-5A, the Asp-282-Cys-283 peptide bond, which is
the predicted ligand-binding site on the C-terminal P domain, is a normal trans
bond, unlike the cases of the other two proteins. The trimeric formation of FD1
results in the separation of the three P domains, and the spatial arrangement of
the three predicted ligand-binding sites on the trimer is very similar to that
of the trimeric collectin, indicating that such an arrangement is generally
required for pathogen-recognition. The ligand binding study of FD1 in solution
indicated that the recombinant protein binds to N-acetyl-d-glucosamine and the
peptide Gly-Pro-Arg-Pro and suggested that the ligand-binding region exhibits a
conformational equilibrium involving cis-trans isomerization of the
Asp-282-Cys-283 peptide bond. The crystal structure and the ligand binding study
of FD1 provide an insight of the self- and non-self discrimination mechanism by
ficolins.
|
|
|
|
|
|
|
|
Figure 3.
FIGURE 3. The conserved disulfide bond and Ca^2+-binding
region in the P domain. A, the Ca^2+-binding loop is stabilized
by the conserved disulfide bond between Cys-270 and Cys-283. B,
the 2F^o - F^c electron density is contoured at 1  at the
region between Asp-282 and His-284. The Asp-282–Cys-283
peptide bond is in the normal trans configuration (arrow). C,
the 2F^o - F^c electron density is contoured at 1.7 at the
calcium-binding site. The Ca^2+ is shown as a yellow sphere.
|
|
Figure 6.
FIGURE 6. Arrangements of the ligand-binding sites of FD1
and MBL. Top (A) and side (B) views of arrangements of the
ligand-binding sites on the FD1 trimer (magenta) and rat MBL
(Protein Data Bank code 1KWV (48); slate). His-284, located on
the predicted ligand-binding site in FD1, and the bound GlcNAc
in rat MBL are shown as green spheres. The three binding sites
of each trimer sit on the vertices of an equilateral triangle
with each side about 50 Å in length.
|
|
|
|
|
|
The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2007,
282,
3889-3895)
copyright 2007.
|
|
|
|
|
|
|
