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PDBsum entry 2vsd
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Immune system receptor
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PDB id
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2vsd
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References listed in PDB file
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Key reference
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Title
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The crystal structure of chir-Ab1: a primordial avian classical fc receptor.
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Authors
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T.I.Arnon,
J.T.Kaiser,
A.P.West,
R.Olson,
R.Diskin,
B.C.Viertlboeck,
T.W.Göbel,
P.J.Bjorkman.
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Ref.
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J Mol Biol, 2008,
381,
1012-1024.
[DOI no: ]
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PubMed id
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Abstract
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CHIR-AB1 is a newly identified avian immunoglobulin (Ig) receptor that includes
both activating and inhibitory motifs and was therefore classified as a
potentially bifunctional receptor. Recently, CHIR-AB1 was shown to bind the Fc
region of chicken IgY and to induce calcium mobilization via association with
the common gamma-chain, a subunit that transmits signals upon ligation of many
different immunoreceptors. Here we describe the 1.8-A-resolution crystal
structure of the CHIR-AB1 ectodomain. The receptor ectodomain consists of a
single C2-type Ig domain resembling the Ig-like domains found in mammalian Fc
receptors such as FcgammaRs and FcalphaRI. Unlike these receptors and other
monomeric Ig superfamily members, CHIR-AB1 crystallized as a 2-fold symmetrical
homodimer that bears no resemblance to variable or constant region dimers in an
antibody. Analytical ultracentrifugation demonstrated that CHIR-AB1 exists as a
mixture of monomers and dimers in solution, and equilibrium gel filtration
revealed a 2:1 receptor/ligand binding stoichiometry. Measurement of the 1:1
CHIR-AB1/IgY interaction affinity indicates a relatively low affinity complex,
but a 2:1 CHIR-AB1/IgY interaction allows an increase in apparent affinity due
to avidity effects when the receptor is tethered to a surface. Taken together,
these results add to the structural understanding of Fc receptors and their
functional mechanisms.
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Figure 2.
Fig. 2. The dimer interface. (a) Dimerization interface
region with one subunit as a surface representation (hydrophilic
contact residues in light blue and hydrophobic contact residues
in green) and the other subunit as transparent ribbon diagram
colored as in Fig. 1b (β-strands A, B, and E are shown in blue;
strands CC′FGG′ are shown in red; a 3[10] helix is shown in
purple; and loops are shown in gray). Strands are labeled in
white, and contact residues are shown as sticks. (b) Cross
section of the dimer interface illustrating the two symmetrical
intersubunit salt bridges (green lines) between Asp44 and Arg72.
Water molecules (yellow spheres) that mediate a hydrogen bond
network (yellow dotted line) between the Gln34 residues of each
subunit are also shown. Strands are labeled in white and colored
as described above. (c) Proposed orientation of a CHIR-AB1 dimer
on a membrane (gray line). Monomers are colored as in Fig. 1b.
The 2-fold symmetry axis relating the monomers is indicated by a
vertical green dotted arrow on the plane of the page. The
distance between the C-terminus of each ectodomain (45 Å)
and the approximate length of the ectodomain (  vert,
similar 35 Å) is indicated (black dashed lines). The
eight-residue stem region connecting each ectodomain subunit to
the transmembrane region is shown as a broken black bar with a
maximum theoretical length of vert,
similar 30 Å (calculated assuming 3.8 Å per
residue). (d) Molecular surfaces of the two subunits in a
CHIR-AB1 dimer, with colors highlighting the electrostatic
potential calculated with APBS tools.^24 Electrostatic potential
is plotted from − 11.2 kT/e (electronegative; red) to + 11.2
kT/e (electropositive; blue), with white indicating
electroneutrality. The right monomer is related to the left
monomer by a rotation about the indicated axis of vert,
similar 170°. Black arrows point toward contact partner
residues.
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Figure 5.
Fig. 5. Models for the CHIR-AB1/FcY interaction. (a) Sequence
alignment of the extracellular domains of CHIR-AB1 and CHIR AB2
with the D1 domains of CHIR-A2, CHIR-B2, and CHIR-AB3 (GenBank
accession numbers AJ745094, AJ745095, AJ745093, AJ639837, and
AJ879909, respectively). Residues at the dimer interface of
CHIR-AB1 are indicated by asterisks above the sequence. (b) The
ribbon diagram of a CHIR-AB1 dimer with residues that differ
from CHIR-AB2 is highlighted as red (dimer interface residues)
or blue (all others) sticks. The highlighted amino acids are
labeled. (c) Potential models for binding between CHIR-AB1 and
IgY. The CHIR-AB1 ectodomain is in blue, the ITIM in the
cytoplasmic tail is represented by a rectangle, and the cell
membrane is shown as a dotted black line. IgY is shown with a
yellow and orange Fc region and gray Fab. Left: A dimer of
CHIR-AB1 is bound asymmetrically to the lower hinge region
between the C[H]2 and the C[H]3 domains of FcY, analogous to the
binding of FcγRs and FcεRI to Fcs. Middle: CHIR-AB1 monomers
bind to the C[H]3–C[H]4 interdomain interface to create a
symmetrical 2:1 complex, analogous to the binding of FcαRI to
Fc. Right: The 2-fold symmetry axis of a CHIR-AB1 dimer aligns
with the 2-fold symmetry axis of FcY to form a symmetrical 2:1
complex in which each CHIR-AB1 monomer binds to the bottom of a
FcY C[H]4 domain.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2008,
381,
1012-1024)
copyright 2008.
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