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Figure 4.
Figure 4. Mechanism of Proline-Rich Peptide Recognition by
EVH1 Domains(A) The peptide ligand (magenta) adopts a
PPII-helical conformation and docks into a V-shaped groove on
the domain surface (green). The orientation shown is
approximately the same as that shown in Figure 3A.(B) Close-up
bird’s-eye view of peptide ligand docked against the conserved
EVH1 domain aromatic triad (green side chains). PPII-helical
axis of the ligand is oriented vertically.(C) Schematic
comparison of EVH1 complex (same orientation as in [A]) and SH3
complex. Both domains use a series of aromatic side chains
(planar protrusions) for recognition, but their different
arrangement caused the PPII-helical ligand (triangular prism) to
dock in different orientations. SH3 recognition focuses on one
surface of the PPII helix and therefore absolutely requires
prolines at sites labeled 2 and 5. EVH1 recognition focuses more
on the overall shape of the helix and therefore shows only an
overall preference for proline residues at all positions.
Recognition interfaces of WW domains and profilin resemble the
SH3 surface.(D) Region of the Mena EVH1 domain that may interact
with C-terminal acidic residues from ActA-derived ligands. A
highly electropositive region (blue) is found immediately
adjacent to the C terminus of the bound core peptide. Potential
path of the continuing peptide chain is indicated by magenta
spheres. Figure was generated using GRASP, Molscript, and
RASTER3D.
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