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PDBsum entry 1evh
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Contractile protein
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PDB id
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1evh
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structure of the enabled/vasp homology 1 domain-Peptide complex: a key component in the spatial control of actin assembly.
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Authors
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K.E.Prehoda,
D.J.Lee,
W.A.Lim.
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Ref.
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Cell, 1999,
97,
471-480.
[DOI no: ]
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PubMed id
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Abstract
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The Enabled/VASP homology 1 (EVH1; also called WH1) domain is an interaction
module found in several proteins implicated in actin-based cell motility. EVH1
domains bind the consensus proline-rich motif FPPPP and are required for
targeting the actin assembly machinery to sites of cytoskeletal remodeling. The
crystal structure of the mammalian Enabled (Mena) EVH1 domain complexed with a
peptide ligand reveals a mechanism of recognition distinct from that used by
other proline-binding modules. The EVH1 domain fold is unexpectedly similar to
that of the pleckstrin homology domain, a membrane localization module. This
finding demonstrates the functional plasticity of the pleckstrin homology fold
as a binding scaffold and suggests that membrane association may play an
auxiliary role in EVH1 targeting.
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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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Figure 6.
Figure 6. Possible Mechanism for EVH1 Domain Targeting of
Actin Assembly(A) EVH1 proteins may recognize proline-rich
peptides (solid rectangle) in an acidic phospholipid context to
selectively localize to leading edge membrane sites.(B)
Pathogens such as Listeria monocytogenes may use peptide ligand
sequences that emulate the combination of interactions described
in (A). The ActA sequences have a high density of negatively
charged residues immediately C-terminal to the peptide’s
proline-rich core peptide sequence. Such ligands have higher
affinity than host-derived ligands and may constitutively
recruit EVH1 domain proteins in a nonmembrane context (e.g.,
outside of the cell wall of the gram-positive bacteria).
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The above figures are
reprinted
by permission from Cell Press:
Cell
(1999,
97,
471-480)
copyright 1999.
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