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Figure 2.
Figure 2. Distinct Binding Modes of SH3-3 and LIM4
Domains(A) Sequence alignment for SH3-3 and LIM4 with other
representative homologs. For representative SH3 domains, CSK
(Ghose et al., 2001), p67^phox (Kami et al., 2002), and ScPex13P
(Pires et al., 2003) were chosen based on the fact that
their crystal structures are available for comparison and that
the former two recognize conventional PXXP motifs and the last
recognizes a nonconventional sequence. Note that the recognition
sequences for Csk and p67phox are not in Table 2 (only non-PxxP
binding sequences are in Table 2). Also, although residues
marked in blue are essential for PXXP binding, other neighboring
residues in the sequence could be potentially involved in
binding to immediate regions of the N or C terminus of the PXXP
ligand. For the LIM domain, PINCH LIM1 and LMO4 were chosen
because their binding modes have been published (Velyvis et al.
2001; Velyvis et al. 2003 and Deane et al. 2003). The binding
interface residues for Nck-2 SH3-3 are marked in red and are
contrasted to conventional PxxP binding sites in CSK_Hum and
p67^phox_Hum (blue), nonconventional binding sites in CSK_Hum
and p67^phox_Hum (orange), and ScPex13P (magenta). The binding
interface residues for PINCH-1 LIM4 are marked in red and are
contrasted to those in PINCH-1 LIM1 and LMO4 (green).(B) The
conventional and nonconventional binding site residues for SH3
domains in (A) are projected to the SH3-3 surface. PPII:
conventional PxxP ligand binding site. Both CSK and p67phox SH3
domains have conventional and nonconventional binding sites.
ScPex13P SH3 has an entirely nonconventional binding mode
(magenta), which is better seen by rotating the surface 90°
counterclockwise around the z axis. However, all of these
binding sites are different from the Nck-2 SH3-3 binding site by
LIM4.(C) The binding site residues for the LIM domains in (A)
are projected to the PINCH-1 LIM4 surface, showing that the LIM4
binding site for SH3-3 is distinct from those of LMO4 and
PINCH-1 LIM1.
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