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PDBsum entry 2rcj
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Immune system
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PDB id
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2rcj
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Contents |
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(+ 4 more)
218 a.a.*
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(+ 4 more)
523 a.a.*
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104 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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Solution structure of human and mouse immunoglobulin m by synchrotron X-Ray scattering and molecular graphics modelling. A possible mechanism for complement activation.
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Authors
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S.J.Perkins,
A.S.Nealis,
B.J.Sutton,
A.Feinstein.
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Ref.
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J Mol Biol, 1991,
221,
1345-1366.
[DOI no: ]
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PubMed id
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Abstract
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The pentameric 71-domain structure of human and mouse immunoglobulin M (IgM) was
investigated by synchrotron X-ray solution scattering and molecular graphics
modelling. The radii of gyration RG of human IgM Quaife and its Fc5, IgM-S,
Fab'2 and Fab fragments were determined as 12.2 nm, 6.1 nm, 6.1 nm, 4.9 nm and
2.9 nm in that order. The RG values were similar for mouse IgM P8 and its Fab'2
and Fab fragments, despite the presence of an additional carbohydrate site. The
IgM scattering curves, to a nominal resolution of 5 nm, were compared with
molecular graphics models based on published crystallographic alpha-carbon
co-ordinates for the Fab and Fc structures of IgG. Good curve fits for Fab were
obtained based on the crystal structure of Fab from IgG. A good curve fit was
obtained for Fab'2, if the two Fab arms were positioned close together at their
contact with the C mu 2 domains. The addition of the Fc fragment close to the C
mu 2 domains of this Fab'2 model, to give a planar structure, accounted for the
scattering curve of IgM-S. The Fc5 fragment was best modelled by a ring of five
Fc monomers, constrained by packing considerations and disulphide bridge
formation. A position for the J chain between two C mu 4 domains rather than at
the centre of Fc5 was preferred. The intact IgM structure was best modelled
using a planar arrangement of these Fab'2 and Fc5 models, with the side-to-side
displacement of the Fab'2 arms in the plane of the IgM structure. All these
models were consistent with hydrodynamic simulations of sedimentation data. The
solution structure of IgM can therefore be reproduced quantitatively in terms of
crystallographic structures for the fragments of IgG. Putative Clq binding sites
have been identified on the C mu 3 domain. These would become accessible for
interaction with Clq when the Fab'2 arms move out of the plane of the Fc5 disc
in IgM, that is, a steric mechanism exposing pre-existing Clq sites. Comparison
with a solution structure for Clq by neutron scattering shows that two or more
of the six globular Clq heads in the hexameric head-and-stalk structure are
readily able to make contacts with the putative Clq sites in the C mu 3 domains
of free IgM if if the Clq arm-axis angle in solution is reduced from 40
degrees-45 degrees to 28 degrees. This could be the trigger for Cl activation.
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Figure 2.
Figure 2. A diagram of the j-sheet topology in the
immunoglobulin fold of onstant domain. The 7
a-strands are labelled using the letters A to G in the
Oxford convention (Williams & Barclay, 1988), and the
letters X and Y in the Cambridge convention Beale &
Feinstein, 1976). The intradomain disulphide bridge
within each Ig fold (Fig. 1) connects he strands fx2 (B)
and fy2 (F). The 6 bends are numbered bl to b6 in the
Cambridge convention.
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Figure 8.
Figure 8. Location f residues implicated in the ossible binding f Cl q to 1gM. (a) Thr posItions of His430. Aspi(:l~~
432 and Pro436 (0) (see the t,ext) lie on the periphery of te Fc, disc. The relationship between 2 adjac-rnt Fc urlits of
the pentamer shows how ys414 ( n ) is able to form disulphide bridges between them. Pairs ofcarbohydrat. sitt, rrsidur+
(A) at .4sn395 and Asn402 are shown for each Cp3 chain. (b) Face-on nd (c) side-o views of the structure seen in (a).
t)ogethcr with a d-arm representation of Clq in contact with the rgion of His430. Asp/(:lu432 and I'ro436. In (b). (`I q is
shown below the plane of t,he Fc Aructure. A Clq arm--axis angle of 28'' is required for c@irnal contacT hrtw-wn r' (`lq
heads in the region of he shaded spheres and 2 adjacent Cl q sites on Fc indicated by 3 (a). It may hr seen that he (`1 q
head must, in part at least, lie within te plane of the Fc, disc. The Debye model for I q is taken from Prrkins (1985).
Figs 8 and 9 were created using INSIGHT TI (Biosym Inca., San Diego. (`4. I:.S.A.) c,n a Silicon ;raphics -CD%`lY~
\Vorkstation.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1991,
221,
1345-1366)
copyright 1991.
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Secondary reference #1
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Title
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Implications of the near-Planar solution structure of human myeloma dimeric iga1 for mucosal immunity and iga nephropathy.
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Authors
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A.Bonner,
P.B.Furtado,
A.Almogren,
M.A.Kerr,
S.J.Perkins.
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Ref.
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J Immunol, 2008,
180,
1008-1018.
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PubMed id
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Headers
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