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PDBsum entry 1zvd
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References listed in PDB file
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Key reference
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Title
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Regulation of smurf2 ubiquitin ligase activity by anchoring the e2 to the hect domain.
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Authors
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A.A.Ogunjimi,
D.J.Briant,
N.Pece-Barbara,
C.Le roy,
G.M.Di guglielmo,
P.Kavsak,
R.K.Rasmussen,
B.T.Seet,
F.Sicheri,
J.L.Wrana.
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Ref.
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Mol Cell, 2005,
19,
297-308.
[DOI no: ]
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PubMed id
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Abstract
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The conjugation of ubiquitin to proteins involves a cascade of activating (E1),
conjugating (E2), and ubiquitin-ligating (E3) type enzymes that commonly signal
protein destruction. In TGFbeta signaling the inhibitory protein Smad7 recruits
Smurf2, an E3 of the C2-WW-HECT domain class, to the TGFbeta receptor complex to
facilitate receptor degradation. Here, we demonstrate that the amino-terminal
domain (NTD) of Smad7 stimulates Smurf activity by recruiting the E2, UbcH7, to
the HECT domain. A 2.1 A resolution X-ray crystal structure of the Smurf2 HECT
domain reveals that it has a suboptimal E2 binding pocket that could be
optimized by mutagenesis to generate a HECT domain that functions independently
of Smad7 and potently inhibits TGFbeta signaling. Thus, E2 enzyme recognition by
an E3 HECT enzyme is not constitutively competent and provides a point of
control for regulating the ubiquitin ligase activity through the action of
auxiliary proteins.
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Figure 4.
Figure 4. UbcH7 Interaction with a Leucine-Rich Repeat in
the NTD of Smad7
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Figure 5.
Figure 5. Crystal Structure of Smurf2 HECT Domain
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The above figures are
reprinted
by permission from Cell Press:
Mol Cell
(2005,
19,
297-308)
copyright 2005.
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