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PDBsum entry 2ddu
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Signaling protein
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PDB id
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2ddu
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References listed in PDB file
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Key reference
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Title
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Structure of a signaling-Competent reelin fragment revealed by X-Ray crystallography and electron tomography.
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Authors
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T.Nogi,
N.Yasui,
M.Hattori,
K.Iwasaki,
J.Takagi.
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Ref.
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EMBO J, 2006,
25,
3675-3683.
[DOI no: ]
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PubMed id
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Abstract
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The large extracellular glycoprotein reelin directs neuronal migration during
brain development and plays a fundamental role in layer formation. It is
composed of eight tandem repeats of an approximately 380-residue unit, termed
the reelin repeat, which has a central epidermal growth factor (EGF) module
flanked by two homologous subrepeats with no obvious sequence similarity to
proteins of known structure. The 2.05 A crystal structure of the mouse reelin
repeat 3 reveals that the subrepeat assumes a beta-jelly-roll fold with
unexpected structural similarity to carbohydrate-binding domains. Despite the
interruption by the EGF module, the two subdomains make direct contact,
resulting in a compact overall structure. Electron micrographs of a four-domain
fragment encompassing repeats 3-6, which is capable of inducing Disabled-1
phosphorylation in neurons, show a rod-like shape. Furthermore, a
three-dimensional molecular envelope of the fragment obtained by single-particle
tomography can be fitted with four concatenated repeat 3 atomic structures,
providing the first glimpse of the structural unit for this important signaling
molecule.
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Figure 2.
Figure 2 Structure of reelin repeat 3. (A) Stereo presentation
of repeat 3. Subdomains are differently colored: subrepeat A
(cyan), EGF (green), and subrepeat B (magenta). Bound calcium
ion and disulfide bridges are shown as a gold sphere and yellow
stick model, respectively. In subrepeat A, segments missing in
the final model owing to poor electron density are indicated by
dotted lines. (B) Stereo diagram of weighted 2|F[0]|-|F[C]|
electron density map in the region corresponding to the Asp-box
motif. Figures were prepared with MOLSCRIPT (Kraulis, 1991),
CONSCRIPT (Lawrence and Bourke, 2000), and RASTER3D (Merritt and
Bacon, 1997).
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Figure 4.
Figure 4 Similarity between the reelin subrepeat and the CBM.
(A) Reelin subrepeat B (R3B) and the ligand-binding domain of
bacterial cellulase (1GWL), in surface presentation, viewed from
the same orientation. Their surfaces are color-coded by the type
of residue: red for acidic, blue for basic, and yellow for
aromatic residues. In 1GWL, its bound ligand oligomannose is
shown in a stick model, whereas in R3B the 'ligand-like'
inserted loop from the subrepeat A, with important residues
making direct side-chain contacts, is shown. (B) Stereo
presentation of the close-up view at the subrepeat A–B
interface. R3B residues involved in the recognition of R3A loop
are shown in stick models inside the half-transparent molecular
surface and labeled. Both hydrophobic and hydrogen bonding
interactions are evident. The figure was made using PyMol
(DeLano, 2002).
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
EMBO J
(2006,
25,
3675-3683)
copyright 2006.
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