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PDBsum entry 3cve
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Signaling protein
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PDB id
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3cve
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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 postsynaptic density proteins homer and shank form a polymeric network structure.
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Authors
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M.K.Hayashi,
C.Tang,
C.Verpelli,
R.Narayanan,
M.H.Stearns,
R.M.Xu,
H.Li,
C.Sala,
Y.Hayashi.
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Ref.
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Cell, 2009,
137,
159-171.
[DOI no: ]
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PubMed id
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Abstract
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The postsynaptic density (PSD) is crucial for synaptic functions, but the
molecular architecture retaining its structure and components remains elusive.
Homer and Shank are among the most abundant scaffolding proteins in the PSD,
working synergistically for maturation of dendritic spines. Here, we demonstrate
that Homer and Shank, together, form a mesh-like matrix structure.
Crystallographic analysis of this region revealed a pair of parallel dimeric
coiled coils intercalated in a tail-to-tail fashion to form a tetramer, giving
rise to the unique configuration of a pair of N-terminal EVH1 domains at each
end of the coiled coil. In neurons, the tetramerization is required for
structural integrity of the dendritic spines and recruitment of proteins to
synapses. We propose that the Homer-Shank complex serves as a structural
framework and as an assembly platform for other PSD proteins.
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Figure 3.
Figure 3. Crystal Structure of the Homer Coiled-Coil Region
(A) Ribbon representation of the crystal structure of the
C-terminal half of Homer1b coiled-coil region CC2. The four
strands are marked A–D.
(B) A model of the whole
structure of long form of Homer. The model is constructed from
the structure of the Homer1CC2 domain (blue), EVH1 domain (red)
(Irie et al., 2002), and coiled-coil probability prediction and
protease degradation sites (Hayashi et al., 2006). The CC1 and a
part of the CC2 domain, whose atomic structures are not known,
are in light green and light blue, respectively. Regions likely
to be disordered are shown in gray.
(C) Primary sequence of
the crystallized fragment. 1B, rat Homer1b; 3A, human Homer3a.
Orange, aliphatic residues (I, L, V); blue, acidic (D, E);
green, basic (K, R); gray, residues not in crystals. Mutations
made in dimeric Homer1b I332R/I337E are shown below.
“abcdefg” denotes positions in the heptad of coiled coil.
(D) Distance between the A and the B strand or between the
C and the D strand are measured and plotted against the number
of residues.
(E) Helical wheel representation of the
dimeric (top) and tetrameric (bottom) region of Homer1b.
Residues start from K290 at g position. Residues that make
knobs-into-holes interactions with residues on the other strands
are shown in blue. Residues changed in the dimeric mutant (I332
and I337) are shown in red. Residues outside the dotted circles
are located within the wide dimeric region.
(F) Example of
intermolecular salt bridges formed between residues at the e
(E295 and E302) and g (K290 and R297) positions within the
dimeric region.
(G) Large amino acids occupying the a and d
positions in the wide dimeric region, Q319 and F322.
(H)
Interchain interactions in the tetrameric region. Residues at d
positions (L329, K336, L343, L350) form the A-D and B-C
interface, and those at e positions (L330, I337, R344, L351)
form the A-C and B-D interface.
(I) Hydrophobic core formed
by leucines at a positions (L326, L333, L340, L347).
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Figure 7.
Figure 7. The Model of Interaction between Homer and Shank
(A) A model of high-order complex between Homer and Shank.
Currently, the oligomeric status of Shank is not known.
(B)
Overlay of the structural model of Homer (blue) on the PSD. The
structure of mGluR1 (yellow) is modeled based on the structure
of mGluR1 extracellular ligand binding domain (Kunishima et al.,
2000) and the structure of rhodopsin (Palczewski et al., 2000).
The structures of IP3R (red) (Sato et al., 2004), TRPC (green)
(Mio et al., 2007), and dynamin (Mears et al., 2007) are taken
from electron microscopy images. All structures are depicted to
scale on an electron microscope image of a hippocampal CA1 spine
with smooth endoplasmic reticulum, obtained and modified from
Spacek and Harris (1997). Copyright 1997 by the Society for
Neuroscience. The presynaptic terminal (Pre), postsynaptic
terminal (Post), and endoplasmic reticulum (ER) are indicated.
Scale bar, 0.1 μm.
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The above figures are
reprinted
by permission from Cell Press:
Cell
(2009,
137,
159-171)
copyright 2009.
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