 |
PDBsum entry 1t83
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Immune system
|
PDB id
|
|
|
|
1t83
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
The structure of a human type III fcgamma receptor in complex with fc.
|
|
|
Authors
|
|
S.Radaev,
S.Motyka,
W.H.Fridman,
C.Sautes-Fridman,
P.D.Sun.
|
|
|
Ref.
|
|
J Biol Chem, 2001,
276,
16469-16477.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Fcgamma receptors mediate antibody-dependent inflammatory responses and
cytotoxicity as well as certain autoimmune dysfunctions. Here we report the
crystal structure of a human Fc receptor (FcgammaRIIIB) in complex with an Fc
fragment of human IgG1 determined from orthorhombic and hexagonal crystal forms
at 3.0- and 3.5-A resolution, respectively. The refined structures from the two
crystal forms are nearly identical with no significant discrepancies between the
coordinates. Regions of the C-terminal domain of FcgammaRIII, including the BC,
C'E, FG loops, and the C' beta-strand, bind asymmetrically to the lower hinge
region, residues Leu(234)-Pro(238), of both Fc chains creating a 1:1
receptor-ligand stoichiometry. Minor conformational changes are observed in both
the receptor and Fc upon complex formation. Hydrophobic residues, hydrogen
bonds, and salt bridges are distributed throughout the receptor.Fc interface.
Sequence comparisons of the receptor-ligand interface residues suggest a
conserved binding mode common to all members of immunoglobulin-like Fc
receptors. Structural comparison between FcgammaRIII.Fc and FcepsilonRI.Fc
complexes highlights the differences in ligand recognition between the high and
low affinity receptors. Although not in direct contact with the receptor, the
carbohydrate attached to the conserved glycosylation residue Asn(297) on Fc may
stabilize the conformation of the receptor-binding epitope on Fc. An
antibody-FcgammaRIII model suggests two possible ligand-induced receptor
aggregations.
|
|
|
|
|
|
|
|
Figure 6.
Fig. 6. Antibody-Fc  RIII
binding and ligand induced receptor aggregation model. A, an
intact antibody-Fc RIII
binding model. The structure of the antibody is shown in magenta
and that of Fc RIII is in
green. The position of the second possible orientation of Fc
RIII, which
is in direct steric conflict with the hinge region and Fab, is
indicated by a blue-shaded area. The arrow points to the
location of the lower hinge (L.H.). The Protein Data Bank entry
for the antibody coordinates is 1IGT. B, a simple avidity model
of antigen-antibody binding induced Fc RIII
aggregation. C, an ordered receptor aggregation model.
|
|
Figure 7.
Fig. 7. Recognition of Fc by multiple ligands. Structural
comparison among the complexes of (A) Fc RIIIB-Fc;
(B) FcRn-Fc (PDB entry 1FRT); (C) rheumatoid factors RF-Fc (PDB
entry 1ADQ); and (D) bacterial protein A-Fc (PDB entry 1FC2).
Protein G binds similar to Fc as does protein A. Due to its
symmetric interaction with ligand, only one chain of Fc is shown
in the FcRn·Fc, RF·Fc and protein A·Fc
complexes. The corresponding Fc regions are colored in cyan and
shown in similar orientations. The ligands to Fc are colored in
green and the  [2]-microglobulin
of FcRn is shown in red. Only the variable domain of RF is
shown. The carbohydrates are shown in ball-and-stick models.
|
|
|
|
|
|
The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2001,
276,
16469-16477)
copyright 2001.
|
|
|
|
|
|
|
