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Figure 4.
Figure 4. SH2 Domain and Dimer Interface(A) Comparison of
the Dd-STATa (yellow) and STAT3 (green) SH2 domains. The
Dd-STATa tail segment is in magenta; that of STAT3 is
transparent. The Dd-STATa SH2 domain shares similar sequence
identity with the mammalian STATs (18%–22%) as with Src (22%),
but a common core of 65 residues is structurally more similar to
Src (rmsd[Cα] = 1.13 Å) than to STAT1 (1.27Å) or
STAT3 (1.47 Å).(B) Overview of the dimer interface. The
view is roughly along the dyad but flipped relative to Figure
3B. The molecular surface and regions of negative (red) and
positive (blue) potential are shown for monomer 2. The
phosphotyrosine phosphate interacts with three Arg residues
(lower right) and is highly buried (upper left). Arg693 is
hydrogen bonded to Glu703 and to the backbone carbonyl of
Ala695. This figure and Figure 5D were made with GRASP (Nicholls
et al., 1991).(C) SH2-P interactions. The view is roughly that
of monomer 1 in (B). Hydrogen bonds (dashed lines) are shown in
black if common to class I SH2 domains, and in red otherwise.
Interactions common to class I domains include phosphotyrosine
recognition by Arg594, Arg612, and Ser614; a hydrogen bond
between the backbone atoms of His636 (data not shown) and
Glu703; and one between Arg594 and the backbone carbonyl of
Gly701. Also common is the hydrophobic binding pocket for Leu705
(pY+3), which in Dd-STATa is formed by residues Tyr637, Phe654,
His658, and Phe661. Interactions unique to Dd-STATa include
those involving Arg616 (see text), a hydrogen bond from Lys635
to the carbonyl of Leu705, a salt bridge between Arg633 and
Glu703, and a van der Waals contact between Gln660 and Asn706.
For clarity, the side chain of Ser707 is omitted.(D) SH2-SH2
interactions viewed along the dyad axis. Side chains mediating
SH2-SH2 contacts are in green (monomer 1) or yellow (monomer 2).
Also shown are BG loop residues His658 and Phe661 (in gray)
which interact with Leu705, and the hydrogen bond between the
backbone of Glu657 and Asn706. For clarity, the side chain of
Asn706 is in transparent form, and those of residues 629–630
are omitted.
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