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PDBsum entry 2dyf
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Protein binding
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PDB id
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2dyf
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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 fbp11 ww1-Pl ligand complex reveals the mechanism of proline-Rich ligand recognition by group ii/III ww domains.
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Authors
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Y.Kato,
T.Miyakawa,
J.Kurita,
M.Tanokura.
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Ref.
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J Biol Chem, 2006,
281,
40321-40329.
[DOI no: ]
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PubMed id
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Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
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Abstract
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FBP11/HYPA is a mammalian homologue of yeast splicing factor Prp40. The first WW
domain of FBP11/HYPA (FBP11 WW1) is essential for preventing severe neurological
diseases such as Huntington disease and Rett syndrome and strongly resembles the
WW domain of FCA, the essential regulator for flowering time control. We have
solved the structure of FBP11 WW1 and a Pro-Pro-Leu-Pro ligand complex, and
demonstrated the binding mechanism with mutational analysis using surface
plasmon resonance. The overall structure of FBP11 WW1 in the complex form is
quite similar to the structures of WW domains from Group I and IV in complexes.
In addition, conformation of FBP11 WW1 does not change much upon ligand binding.
The binding orientation of the ligand against FBP11 WW1 is the same as that of
the Group IV WW domain-ligand complex, but opposite to that of the Group I
complex. The ligand interacts with two grooves formed by surface aromatic
residues. The Pro and Leu residues in the ligand interact with the grooves and
the Loop I region of FBP11 WW1, respectively, which are necessary interactions
for binding the ligand. Interestingly, the two aromatic grooves recognize the
Pro residues in entirely different manners, which allows FBP11 WW1 to recognize
shorter sequences than the SH3 domain. Combined with homology models of other WW
domains, the present report shows the detailed mechanism of ligand binding by
Group II/III WW domains, and provides information useful in designing drugs to
treat neurodegenerative diseases.
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Figure 1.
FIGURE 1. Superimposition of 20 output structures from
CYANA-2.0. Backbones of FBP11 WW1 and the PL ligand are
represented in navy and salmon pink, respectively. Side chains
of the ligand are colored in red. Pink side chains of FBP11 WW1
are in contact with the ligand, whereas purple ones form a small
hydrophobic core. Thr-13 is shown in orange, although it is not
in contact with the ligand in our structure.
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Figure 2.
FIGURE 2. Configuration and model of the complex of FBP11
WW1 and the PL motif. A, the backbone of FBP11 WW1 is
represented by a ribbon with some important side chains, and the
PL ligand is depicted as wires. Side chains in magenta are in
direct contact with the ligand. Wire in pale blue is the
backbone of the ligand flanked with its side chains in
yellow-green. The side chain of Thr-13 is again shown in orange.
B, the surface of FBP11 WW1 is represented with the PL ligand
depicted as a yellow wire. The XP groove, XP2 groove, and
Ali-patch are circled with blue, navy, and green-yellow ovals,
respectively. Surface representation and calculation of
electrostatic potential is carried out using MOLMOL (36). The
kT/e range of electrostatic surface shading is from -1.0 (red)
to +1.0 (blue). C, schematic model of the ligand-binding
mechanism of FBP11 WW1 to a Pro-rich ligand that forms the PPII
helix. The numbering of residues corresponds to the PL motif
ligand of our structure. The crosshatched surface on the XP
groove is a part of the Ali-patch. Pro-5' is recognized in a
perpendicular manner by the XP2 groove, whereas the XP groove
grasps the Leu-7' to Pro-8' sequence in parallel with the Trp-34
plane. The side chain of Pro-6' comes in contact with an edge of
the XP2 groove. The two grooves of FBP11 WW1 primarily recognize
four successive residues. D, the binding mechanism of SH3
domains to a Pro-rich ligand forming the PPII helix (37). In
contrast to FBP11 WW1, both XP grooves align in parallel and
recognize the respective Xaa-Pro sequences in a parallel manner.
In addition, the SH3 domains do not recognize a residue
(indicated by green asterisk) lying between two Xaa-Pro
sequences in the ligand.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2006,
281,
40321-40329)
copyright 2006.
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