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PDBsum entry 2djy
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Ligase/signaling protein
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PDB id
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2djy
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References listed in PDB file
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Key reference
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Title
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An expanded ww domain recognition motif revealed by the interaction between smad7 and the e3 ubiquitin ligase smurf2.
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Authors
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P.A.Chong,
H.Lin,
J.L.Wrana,
J.D.Forman-Kay.
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Ref.
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J Biol Chem, 2006,
281,
17069-17075.
[DOI no: ]
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PubMed id
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Abstract
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Smurf2 is an E3 ubiquitin ligase that drives degradation of the transforming
growth factor-beta receptors and other targets. Recognition of the receptors by
Smurf2 is accomplished through an intermediary protein, Smad7. Here we have
demonstrated that the WW3 domain of Smurf2 can directly bind to the Smad7
polyproline-tyrosine (PY) motif. Of particular interest, the highly conserved WW
domain binding site Trp, which interacts with target PY motifs, is a Phe in the
Smurf2 WW3 domain. To examine this interaction, the solution structure of the
complex between the Smad7 PY motif region (ELESPPPPYSRYPMD) and the Smurf2 WW3
domain was determined. The structure reveals that, in addition to binding the PY
motif, the WW3 domain binds six residues C-terminal to the PY motif (PY-tail).
Although the Phe in the WW3 domain binding site decreases affinity relative to
the canonical Trp, this is balanced by additional interactions between the
PY-tail and the beta1-strand and beta1-beta2 loop of the WW3 domain. The
interaction between the Smurf2 WW3 domain and the Smad7 PY motif is the first
example of PY motif recognition by a WW domain with a Phe substituted for the
binding site Trp. This unusual interaction allows the Smurf2 WW3 domain to
recognize a subset of PY motif-containing proteins utilizing an expanded surface
to provide specificity.
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Figure 1.
FIGURE 1. Solution structure of the Smurf2 WW3 domain-Smad7
PY peptide complex. a, superposition of the 30 lowest energy
structures. The WW3 domain backbone is shown in blue and side
chains in turquoise, except for positions typically occupied by
conserved Trp residues, which are in green. The PY peptide
backbone is red with side chains shown in gold. b, ribbon
diagram of the lowest energy structure. The coloring scheme is
as in a, except that WW3 domain loop regions are shown in gray.
Residues designated with a prime symbol (') are Smad7 residues.
For clarity, some side chains are not shown. Figs. 1, 2, 3a, and
5b were generated using MOLMOL (37). N, N terminus; C, C
terminus.
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Figure 2.
FIGURE 2. Superposition of the PY motifs and binding
pockets from the Smad7-Smurf2 WW3 domain complex and the  -dystroglycan-dystrophin
WW domain complex. Smad7 and Smurf2 are shown in red and blue
and -dystroglycan and
dystrophin in black and gray, respectively. Labels in
parentheses indicate residues from the -dystroglycan-dystrophin
complex.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2006,
281,
17069-17075)
copyright 2006.
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