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PDBsum entry 2fcb
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Immune system
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PDB id
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2fcb
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the soluble form of the human fcgamma-Receptor iib: a new member of the immunoglobulin superfamily at 1.7 a resolution.
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Authors
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P.Sondermann,
R.Huber,
U.Jacob.
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Ref.
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Embo J, 1999,
18,
1095-1103.
[DOI no: ]
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PubMed id
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Abstract
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Fcgamma-receptors (FcgammaRs) represent the link between the humoral and
cellular immune responses. Via the binding to FcgammaR-positive cells,
immunocomplexes trigger several functions such as endocytosis,
antibody-dependent cell-mediated cytotoxity (ADCC) and the release of mediators,
making them a valuable target for the modulation of the immune system. We solved
the crystal structure of the soluble human Fcgamma-receptor IIb (sFcgammaRIIb)
to 1.7 A resolution. The structure reveals two typical immunoglobulin (Ig)-like
domains enclosing an angle of approximately 70 degrees, leading to a
heart-shaped overall structure. In contrast to the observed flexible arrangement
of the domains in other members of the Ig superfamily, the two domains are
anchored by several hydrogen bonds. The structure reveals that the residues
relevant for IgG binding, which were already partially characterized by
mutagenesis studies, are located within the BC, C'E and FG loops between the
beta-strands of the second domain. Moreover, we discuss a model for the
sFcgammaRIIb:IgG complex. In this model, two FcgammaR molecules bind one IgG
molecule with their second domains, while the first domain points away from the
complex and is therefore available for binding other cell surface molecules, by
which potential immunosuppressing functions could be mediated.
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Figure 1.
Figure 1 Overall structure of human sFc  RIIb.
Stereo ribbon representation of the sFc RIIb
structure. The loops supposed to be important for IgG binding
are depicted in red with some of the residues within the binding
site and the conserved disulfide bridge in ball and stick
representation. The potential N-glycosylation sites are shown as
green balls. The termini are labelled and the  -strands
are numbered consecutively for the N-terminal domain in black
and for the C-terminal domain in blue. The figure was created
using the programs MOLSCRIPT (Kraulis, 1991) and RENDER (Merritt
and Murphy, 1994).
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Figure 4.
Figure 4 The putative binding sites of Fc RIIb.
Solid-surface representations of Fc RIIb
as produced with GRASP (Nicholls et al., 1991), with colour
coding according to the relative surface potential from negative
(red) to positive (blue). (A) The molecule as in Figure 1 by a
rotation of  90°
counter clockwise around the vertical. (B) The molecule is
rotated 90° clockwise around the same axis. Both views show
the putative binding regions on the C-terminal (A) and the
N-terminal domain (B). The amino acid residues discussed in the
text are labelled.
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
Embo J
(1999,
18,
1095-1103)
copyright 1999.
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