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PDBsum entry 3cm9
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Immune system
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PDB id
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3cm9
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Contents |
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462 a.a.*
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106 a.a.*
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214 a.a.*
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585 a.a.*
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* C-alpha coords only
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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 nonplanar secretory iga2 and near planar secretory iga1 solution structures rationalize their different mucosal immune responses.
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Authors
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A.Bonner,
A.Almogren,
P.B.Furtado,
M.A.Kerr,
S.J.Perkins.
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Ref.
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J Biol Chem, 2009,
284,
5077-5087.
[DOI no: ]
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PubMed id
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Abstract
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Secretory IgA (SIgA) is the most prevalent human antibody and is central to
mucosal immunity. It exists as two subclasses, SIgA1 and SIgA2, where SIgA2 has
a shorter hinge joining the Fab and Fc regions. Both forms of SIgA are
predominantly dimeric and contain an additional protein called the secretory
component (SC) that is attached during the secretory process and is believed to
protect SIgA in harsh mucosal conditions. Here we locate the five SC domains
relative to dimeric IgA2 within SIgA2 using constrained scattering modeling. The
x-ray and sedimentation parameters showed that SIgA2 has an extended solution
structure. The constrained modeling of SIgA2 was initiated using two IgA2
monomers that were positioned according to our best fit solution structure for
dimeric IgA1. SC was best located along the convex edge of the Fc-Fc region. The
best fit models showed that SIgA2 is significantly nonplanar in its structure,
in distinction to our previous near planar SIgA1 structure. Both the shorter
IgA2 hinges and the presence of SC appear to displace the four Fab regions out
of the Fc plane in SIgA2. This may explain the noncovalent binding of SC in some
SIgA2 molecules. This nonplanar structure is predicted to result in specific
immune properties for SIgA2 and SIgA1. It may explain differences observed
between the SIgA1 and SIgA2 subclasses in terms of their interactions with
antigens, susceptibility to proteases, effects on receptors, and distribution in
different tissues. The different structures account for the prevalence of both
forms in mucosal secretions.
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Figure 1.
Domain structure of SIgA2. SIgA2 is shown as two IgA2m(1)
monomers, a J chain, and a secretory component (domains
D1–D5). Each IgA2 heavy chain contains the V[H], C[H]1, C[H]2,
and C[H]3 domains. Each light chain contains the V[L] and C[L]
domains. The complementarity-determining regions (CDR), the
13-residue hinge and the 18-residue C-terminal tailpiece are
highlighted. The IgA2m(2) allotype does not have a
Cys^214–Cys^214 disulfide bridge. The possible interheavy
chain disulfide bridges at Cys^241, Cys^242, Cys^299, and
Cys^301 are denoted by an extended X. Cys^471 in one tailpiece
of each Fc region is disulfide-bridged with either Cys^15 or
Cys^68 in the J chain, which is located on the convex edge of
the Fc-Fc region. A Cys^311–Cys^502 bridge between the C[H]2
and D5 domains is shown. N-Linked oligosaccharide sites are
denoted by filled symbols (•).
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Figure 7.
Survey of best fit models for SIgA2 from Cycle 2. Comparison
of the x-ray R factors with the R[G] and R[XS] values for 3000
models based on the randomization of the Fab regions. The dashed
lines indicate the experimental x-ray R[G], R[XS-1], and
R[XS-2]values.
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The above figures are
reprinted
from an Open Access publication published by the ASBMB:
J Biol Chem
(2009,
284,
5077-5087)
copyright 2009.
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Secondary reference #1
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Title
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Solution structure determination of monomeric human iga2 by X-Ray and neutron scattering, Analytical ultracentrifugation and constrained mdoelling: a comparison with monomeric human iga1
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Authors
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P.B.Furtado,
P.W.Whitty,
A.Robertson,
J.T.Eaton,
A.Almogren,
M.A.Kerr,
J.M.Woof,
S.J.Perkins.
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Ref.
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j mol biol, 2004,
338,
921.
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Secondary reference #2
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Title
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Location of secretory component on the fc edge of dimeric iga1 reveals insight into the role of secretory iga1 in mucosal immunity.
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Authors
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A.Bonner,
A.Almogren,
P.B.Furtado,
M.A.Kerr,
S.J.Perkins.
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Ref.
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Mucosal Immunol, 2009,
2,
74-84.
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
perfect match.
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Headers
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