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Figure 3.
Figure 3. Stereo views showing the binding mode of Pro residues
by the WW domain and comparison to that observed in SH3 domains.
a, Electron density map at the interface between the  -dystroglycan
peptide and the WW and EF-hand domains. The 2F[o] - F[ c] map is
contoured at 1.3  and
was calculated using data to 1.9 Å resolution. The dystrophin
domains and the peptide are colored as in Fig. 1. Note the
interactions of peptide Pro residues with the 'aromatic cradle'
formed by Tyr 3072 and Trp 3083. Residues Trp 3061 and Pro 3086
are highly conserved in WW domains and form the hydrophobic
buckle on the underside of the domain. b, Superposition of the
dystrophin aromatic cradle with a similar recognition element in
the Abl SH3 domain20. The superposition was calculated using
only the proline-rich peptides (residues 887 -890 in the -dystroglycan
peptide, with residues C4 -C7 in the Abl SH3 -peptide complex).
Thin black lines indicate similar hydrogen bond and hydrophobic
interactions. Note that the geometry of interaction with the Trp
residue is essentially identical in the two structures,
including the contact of the Pro with the Trp ring, and the
hydrogen bond to the Trp from the carbonyl group of the 'P-2'
residue (the residue preceeding the first proline by two
positions). The second Pro residue (Pro 890 in -dystroglycan)
makes a van der Waals contact to Ser 3066 that is similar to
that made to a Phe ring in the Abl structure. The interaction of
Pro 890 with the surface of Tyr 3072 is more divergent; the
corresponding surface is formed by a Pro and a Tyr in the SH3
domain. Both SH3 and WW domains have been shown to recognize
non-natural N-substituted amino acids (in addition to Pro) at
particular positions33; the site occupied by Pro 890 is such a
position, and it would likely accommodate small hydrophobic
N-substituted residues.
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