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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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