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PDBsum entry 1gl4
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Basement membrane
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PDB id
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1gl4
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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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Structural basis for the high-Affinity interaction of nidogen-1 with immunoglobulin-Like domain 3 of perlecan.
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Authors
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M.Kvansakul,
M.Hopf,
A.Ries,
R.Timpl,
E.Hohenester.
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Ref.
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EMBO J, 2001,
20,
5342-5346.
[DOI no: ]
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PubMed id
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Abstract
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Nidogen and perlecan are large multifunctional basement membrane (BM) proteins
conserved in all metazoa. Their high-affinity interaction, which is likely to
contribute to BM assembly and function, is mediated by the central G2 domain in
nidogen and the third immunoglobulin (IG)-like domain in perlecan, IG3. We have
solved the crystal structure at 2.0 A resolution of the mouse nidogen-1
G2-perlecan IG3 complex. Perlecan IG3 belongs to the I-set of the IG superfamily
and binds to the wall of the nidogen-1 G2 beta-barrel using beta-strands C, D
and F. Nidogen-1 residues participating in the extensive interface are highly
conserved, whereas the corresponding binding site on perlecan is more variable.
We hypothesize that a second, as yet unidentified, activity of nidogen overlaps
with perlecan binding and accounts for the unusually high degree of surface
conservation in the G2 domain.
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Figure 1.
Figure 1 Domain organization of mouse perlecan (Noonan et al.,
1991) and nidogen-1 (Mann et al., 1989). HS, heparan sulfate
oligosaccharide chains; SEA, domain found in sea urchin sperm
protein, enterokinase, agrin; LA, LDL receptor type A; IG,
immunoglobulin-like; L4, laminin domain IV; LE, laminin type
epidermal growth factor-like; LG, laminin G-like; EG, epidermal
growth factor-like; TY, thyroglobulin-like; G1 -3, nidogen
globular domains. The double-headed arrow indicates the
high-affinity interaction between nidogen-1 G2 (in cyan, with
the preceding EG domain in green) and perlecan IG3 (in magenta).
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Figure 3.
Figure 3 Stereoview of the nidogen-1 G2 -perlecan IG3 interface.
Nidogen-1 and perlecan residues are in cyan and magenta,
respectively, and are labelled, as are  -strands
contributing to the interface. Hydrogen bonds are indicated by
thin black lines. The view direction is similar to the lower
panel in Figure 2A.
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(2001,
20,
5342-5346)
copyright 2001.
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Secondary reference #1
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Title
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Crystal structure and mutational analysis of a perlecan-Binding fragment of nidogen-1.
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Authors
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M.Hopf,
W.Göhring,
A.Ries,
R.Timpl,
E.Hohenester.
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Ref.
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Nat Struct Biol, 2001,
8,
634-640.
[DOI no: ]
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PubMed id
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Figure 1.
Figure 1. The nidogen G2 structure. a, Stereo view of the
structure with the EGF-like domain in green and the -barrel
domain in cyan. -strands
are labeled a -b in the EGF-like domain and A -K in the -barrel
domain. The  -helices
1 -3 are in red and disulfide bridges in yellow. To facilitate
the tracing of the polypeptide chain disordered segments
(residues 357 -366, 374 -380, 565 -570 and 588 -595) have been
included in arbitrary but stereochemically sensible
conformations and are shown in light gray. b, Topology diagram
of the -barrel
domain. The barrel is closed by the parallel interaction of
strands A and F. c, Stereo view of a portion of the experimental
electron density map after solvent flattening at 2.8 Å
resolution. The final model is superimposed on the map. Shown
are -strands
D, E and F. Figs 1a,c, 2 and 4 were made with BOBSCRIPT35 and
RASTER3D^36.
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Figure 2.
Figure 2. Comparison of the  -barrels
of nidogen G2 and Aequora victoria GFP22. Nidogen G2 is in
magenta and GFP in green. A total of 195 C atoms
were superimposed with an r.m.s. deviation of 2.5 Å. In the
nidogen G2 trace every 20^th C atom
is shown as a small, labeled sphere. The chromophore in GFP is
shown as a ball-and-stick model.
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The above figures are
reproduced from the cited reference
with permission from Macmillan Publishers Ltd
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Secondary reference #2
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Title
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Mapping of binding sites for nidogens, Fibulin-2, Fibronectin and heparin to different ig modules of perlecan.
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Authors
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M.Hopf,
W.Göhring,
K.Mann,
R.Timpl.
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Ref.
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J Mol Biol, 2001,
311,
529-541.
[DOI no: ]
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PubMed id
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Figure 3.
Figure 3. Mouse nidogen-1 domain G2 is responsible for the
major binding activity to perlecan fragment IG2-9. Solid-phase
assays were carried out with immobilized IG2-9 and binding of
soluble nidogen ligands was detected by antibodies specific for
nidogen-1. These ligands were nidogen-1 (  open
) and its recombinant fragments NdI (0m), G2 (  triangle,
open ) and NdIII (  ).
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Figure 5.
Figure 5. Localization of different binding sites to mouse
perlecan domain IV (IG2-15). The model is drawn with the
assumption of a disulfide bond connectivity between IG2 and IG13
based on extra cysteine residues[21].
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The above figures are
reproduced from the cited reference
with permission from Elsevier
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