|
Figure 3.
Figure 3. Structure-Based Sequence Alignment and Structural
Comparisons
(A) Structural alignment of murine SOCS3Δ with
the SH2 domains of human Src (PDB code 1SPS) (Waksman et al.,
1993), human SHP2 (N-terminal SH2, PDB code 1AYA) (Lee et al.,
1994), and murine SOCS1 (predicted). Residues shaded in purple
reside in α helices, and residues shaded in cyan reside in β
strands. Disordered residues not included in the atomic model
are italicized. The residues in the BG loop that were deleted in
the SOCS3Δ construct are shaded in gray. Residues of the SOCS3
and SOCS1 kinase inhibitory region are underlined. Residues
colored blue make direct hydrogen bonds or salt bridges via
their side chains to the phosphate group of the bound
phosphopeptide (predicted for SOCS1), and residues colored red
make direct hydrogen bonds via their side chains to other
residues in the bound phosphopeptide (only present in
SOCS3Δ-gp130).
(B) Superposition (Cα trace) of the
SOCS3Δ-gp130(pTyr757) structure with the N-terminal SH2 domain
of SHP2 with bound phosphopeptide (PDB code 1AYA) (Lee et al.,
1994). Residues in βB, βC, and βD were used in the
superposition (rmsd = 0.28 Å for 20 Cα atoms). SOCS3Δ is
colored cyan, the gp130 phosphopeptide is colored yellow, the
SHP2 N-terminal SH2 domain is colored dark green, and the bound
phosphopeptide is colored light green. Select side chains of the
phosphopeptides are shown in stick representation: Val (P−2),
pTyr (P), Val (P+3), and His (P+5) (SOCS3 structure) or Pro
(P+5) (SHP2 structure).
(C) Superposition (Cα trace) of
the SOCS3Δ-gp130(pTyr757) crystal structure and the
SOCS3-gp130(pTyr757) NMR structure (PDB code 2BBU) (Babon et
al., 2006). The individual NMR structure with the lowest overall
rmsd (#18 in the 20-structure ensemble; rmsd = 4.3 Å for
115 Cα atoms) was used for the comparison. For the figure,
residues in βB, βC, and βD were superimposed (rmsd = 1.4
Å for 23 Cα atoms). SOCS3Δ and the gp130 phosphopeptide
from the crystal structure are colored cyan and yellow,
respectively, and SOCS3 and the gp130 phosphopeptide from the
NMR structure are colored dark green and light green,
respectively. For clarity, the  vert,
similar 30 residue PEST sequence at the beginning of the BG loop
has been omitted from the NMR structure. The beginning/end of
the omitted interval are indicated by green arrows, and the
beginning/end of the disordered region of the BG loop in the
SOCS3Δ crystal structure are indicated by cyan arrows. As in
(A), select side chains of the phosphopeptide are shown in stick
representation.
|
