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PDBsum entry 2f3n
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Structural protein
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PDB id
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2f3n
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References listed in PDB file
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Key reference
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Title
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An architectural framework that may lie at the core of the postsynaptic density.
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Authors
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M.K.Baron,
T.M.Boeckers,
B.Vaida,
S.Faham,
M.Gingery,
M.R.Sawaya,
D.Salyer,
E.D.Gundelfinger,
J.U.Bowie.
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Ref.
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Science, 2006,
311,
531-535.
[DOI no: ]
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PubMed id
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Abstract
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The postsynaptic density (PSD) is a complex assembly of proteins associated with
the postsynaptic membrane that organizes neurotransmitter receptors, signaling
pathways, and regulatory elements within a cytoskeletal matrix. Here we show
that the sterile alpha motif domain of rat Shank3/ProSAP2, a master scaffolding
protein located deep within the PSD, can form large sheets composed of helical
fibers stacked side by side. Zn2+, which is found in high concentrations in the
PSD, binds tightly to Shank3 and may regulate assembly. Sheets of the Shank
protein could form a platform for the construction of the PSD complex.
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Figure 1.
Fig. 1. The Shank3 SAM domain forms large sheets of helical
fibers. (A) An EM image of Shank-SAM reveals over 25 fibers
stacked side by side in a two-dimensional sheet. (B) At higher
magnification, the well-ordered nature of the sheet can be seen
as individual subunits that are arranged in a highly ordered
array. (C) The packing of Shank-SAM into a sheet is also evident
in the crystal structure of Shank-SAM M56E (a soluble mutant)
solved to 2.1 Å. Yellow and blue depict fibers stacked in
opposite orientations. Both the antiparallel and parallel
orientations are seen in the crystal, but we believe the
antiparallel orientation is physiologically relevant for several
reasons. First, the interfiber interface buries more surface
area in the antiparallel orientation (1264 Å2 versus 852
Å2). Second, the position of a mutation that solubilizes
the protein (W5E) is in the interface between antiparallel
fibers (Fig. 2C) but not parallel fibers. Finally, Zn2+, which
has a dramatic effect on sheet organization, stabilizes salt
bridges between antiparallel fibers but not parallel fibers
(Fig. 3C). In the numbering scheme used for the crystal
structure, residue 1 corresponds to residue 174 in the full rat
Shank3 sequence.
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Figure 4.
Fig. 4. Assembly mutants prevent the localization of Shank to
the synapse. Visualization of Shank variant distributions in
transfected hippocampal neurons is shown. The wild-type
Shank-416-GFP construct (green) clusters in neuronal dendrites
and colocalizes with Bassoon (red) in transfected hippocampal
neurons (insets: left, GFP; middle, Bassoon; right, merge). In
contrast, mutants (W5E, H22A, M56E, and all three double
mutants) display a diffusely distributed green fluorescence,
indicating no preferential localization to synaptic sites as
indicated by Bassoon staining (insets). F8E shows partial
clustering and partial colocalization with Bassoon (inset).
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The above figures are
reprinted
by permission from the AAAs:
Science
(2006,
311,
531-535)
copyright 2006.
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