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PDBsum entry 1zvd
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Contents |
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* Residue conservation analysis
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PDB id:
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Ligase
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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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Structure:
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Smad ubiquitination regulatory factor 2. Chain: a. Fragment: hect domain. Synonym: ubiquitin-- protein ligase smurf2, smad-specific e3 ubiquitin ligase 2, hsmurf2. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: smurf2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
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Resolution:
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2.10Å
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R-factor:
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0.202
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R-free:
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0.248
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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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Key ref:
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A.A.Ogunjimi
et al.
(2005).
Regulation of Smurf2 ubiquitin ligase activity by anchoring the E2 to the HECT domain.
Mol Cell,
19,
297-308.
PubMed id:
DOI:
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Date:
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01-Jun-05
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Release date:
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09-Aug-05
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PROCHECK
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Headers
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References
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Q9HAU4
(SMUF2_HUMAN) -
E3 ubiquitin-protein ligase SMURF2 from Homo sapiens
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Seq:
Struc:
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748 a.a.
373 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.2.3.2.26
- HECT-type E3 ubiquitin transferase.
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Reaction:
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S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6- ubiquitinyl-[acceptor protein]-L-lysine
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DOI no:
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Mol Cell
19:297-308
(2005)
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PubMed id:
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Regulation of Smurf2 ubiquitin ligase activity by anchoring the E2 to the HECT domain.
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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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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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Selected figure(s)
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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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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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D.Y.Lin,
J.Diao,
D.Zhou,
and
J.Chen
(2011).
Biochemical and structural studies of a HECT-like ubiquitin ligase from Escherichia coli O157:H7.
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J Biol Chem,
286,
441-449.
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PDB codes:
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E.Maspero,
S.Mari,
E.Valentini,
A.Musacchio,
A.Fish,
S.Pasqualato,
and
S.Polo
(2011).
Structure of the HECT:ubiquitin complex and its role in ubiquitin chain elongation.
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EMBO Rep,
12,
342-349.
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PDB codes:
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H.C.Kim,
A.M.Steffen,
M.L.Oldham,
J.Chen,
and
J.M.Huibregtse
(2011).
Structure and function of a HECT domain ubiquitin-binding site.
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EMBO Rep,
12,
334-341.
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PDB code:
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J.H.Hurley,
and
H.Stenmark
(2011).
Molecular mechanisms of ubiquitin-dependent membrane traffic.
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Annu Rev Biophys,
40,
119-142.
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X.Yan,
and
Y.G.Chen
(2011).
Smad7: not only a regulator, but also a cross-talk mediator of TGF-β signalling.
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Biochem J,
434,
1.
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A.A.Ogunjimi,
S.Wiesner,
D.J.Briant,
X.Varelas,
F.Sicheri,
J.Forman-Kay,
and
J.L.Wrana
(2010).
The ubiquitin binding region of the Smurf HECT domain facilitates polyubiquitylation and binding of ubiquitylated substrates.
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J Biol Chem,
285,
6308-6315.
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A.G.Eldridge,
and
T.O'Brien
(2010).
Therapeutic strategies within the ubiquitin proteasome system.
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Cell Death Differ,
17,
4.
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D.C.Scott,
J.K.Monda,
C.R.Grace,
D.M.Duda,
R.W.Kriwacki,
T.Kurz,
and
B.A.Schulman
(2010).
A dual E3 mechanism for Rub1 ligation to Cdc53.
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Mol Cell,
39,
784-796.
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PDB codes:
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P.A.Chong,
H.Lin,
J.L.Wrana,
and
J.D.Forman-Kay
(2010).
Coupling of tandem Smad ubiquitination regulatory factor (Smurf) WW domains modulates target specificity.
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Proc Natl Acad Sci U S A,
107,
18404-18409.
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PDB code:
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R.K.Pandya,
J.R.Partridge,
K.R.Love,
T.U.Schwartz,
and
H.L.Ploegh
(2010).
A structural element within the HUWE1 HECT domain modulates self-ubiquitination and substrate ubiquitination activities.
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J Biol Chem,
285,
5664-5673.
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PDB code:
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S.Li,
K.Lu,
J.Wang,
L.An,
G.Yang,
H.Chen,
Y.Cui,
X.Yin,
P.Xie,
G.Xing,
F.He,
and
L.Zhang
(2010).
Ubiquitin ligase Smurf1 targets TRAF family proteins for ubiquitination and degradation.
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Mol Cell Biochem,
338,
11-17.
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D.Rotin,
and
S.Kumar
(2009).
Physiological functions of the HECT family of ubiquitin ligases.
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Nat Rev Mol Cell Biol,
10,
398-409.
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E.A.Whitcomb,
and
A.Taylor
(2009).
Ubiquitin control of S phase: a new role for the ubiquitin conjugating enzyme, UbcH7.
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Cell Div,
4,
17.
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E.A.Whitcomb,
E.J.Dudek,
Q.Liu,
and
A.Taylor
(2009).
Novel control of S phase of the cell cycle by ubiquitin-conjugating enzyme H7.
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Mol Biol Cell,
20,
1-9.
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H.B.Kamadurai,
J.Souphron,
D.C.Scott,
D.M.Duda,
D.J.Miller,
D.Stringer,
R.C.Piper,
and
B.A.Schulman
(2009).
Insights into ubiquitin transfer cascades from a structure of a UbcH5B approximately ubiquitin-HECT(NEDD4L) complex.
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Mol Cell,
36,
1095-1102.
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PDB codes:
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H.C.Kim,
and
J.M.Huibregtse
(2009).
Polyubiquitination by HECT E3s and the determinants of chain type specificity.
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Mol Cell Biol,
29,
3307-3318.
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J.R.Lee,
A.J.Oestreich,
J.A.Payne,
M.S.Gunawan,
A.P.Norgan,
and
D.J.Katzmann
(2009).
The HECT domain of the ubiquitin ligase Rsp5 contributes to substrate recognition.
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J Biol Chem,
284,
32126-32137.
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J.S.Kang,
C.Liu,
and
R.Derynck
(2009).
New regulatory mechanisms of TGF-beta receptor function.
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Trends Cell Biol,
19,
385-394.
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J.Wang,
and
B.A.Schulman
(2009).
(G2)BRinging an E2 to E3.
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Structure,
17,
916-917.
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K.R.Love,
R.K.Pandya,
E.Spooner,
and
H.L.Ploegh
(2009).
Ubiquitin C-terminal electrophiles are activity-based probes for identification and mechanistic study of ubiquitin conjugating machinery.
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ACS Chem Biol,
4,
275-287.
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M.E.French,
B.R.Kretzmann,
and
L.Hicke
(2009).
Regulation of the RSP5 Ubiquitin Ligase by an Intrinsic Ubiquitin-binding Site.
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J Biol Chem,
284,
12071-12079.
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M.Guzman-Ayala,
K.L.Lee,
K.J.Mavrakis,
P.Goggolidou,
D.P.Norris,
and
V.Episkopou
(2009).
Graded Smad2/3 activation is converted directly into levels of target gene expression in embryonic stem cells.
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PLoS ONE,
4,
e4268.
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M.Narimatsu,
R.Bose,
M.Pye,
L.Zhang,
B.Miller,
P.Ching,
R.Sakuma,
V.Luga,
L.Roncari,
L.Attisano,
and
J.L.Wrana
(2009).
Regulation of planar cell polarity by Smurf ubiquitin ligases.
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Cell,
137,
295-307.
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P.Lönn,
A.Morén,
E.Raja,
M.Dahl,
and
A.Moustakas
(2009).
Regulating the stability of TGFbeta receptors and Smads.
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Cell Res,
19,
21-35.
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T.Mund,
and
H.R.Pelham
(2009).
Control of the activity of WW-HECT domain E3 ubiquitin ligases by NDFIP proteins.
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EMBO Rep,
10,
501-507.
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C.To,
S.Kulkarni,
T.Pawson,
T.Honda,
G.W.Gribble,
M.B.Sporn,
J.L.Wrana,
and
G.M.Di Guglielmo
(2008).
The synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid-imidazolide alters transforming growth factor beta-dependent signaling and cell migration by affecting the cytoskeleton and the polarity complex.
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J Biol Chem,
283,
11700-11713.
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E.C.Osmundson,
D.Ray,
F.E.Moore,
Q.Gao,
G.H.Thomsen,
and
H.Kiyokawa
(2008).
The HECT E3 ligase Smurf2 is required for Mad2-dependent spindle assembly checkpoint.
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J Cell Biol,
183,
267-277.
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J.Diao,
Y.Zhang,
J.M.Huibregtse,
D.Zhou,
and
J.Chen
(2008).
Crystal structure of SopA, a Salmonella effector protein mimicking a eukaryotic ubiquitin ligase.
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Nat Struct Mol Biol,
15,
65-70.
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PDB codes:
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K.H.Wrighton,
and
X.H.Feng
(2008).
To (TGF)beta or not to (TGF)beta: fine-tuning of Smad signaling via post-translational modifications.
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Cell Signal,
20,
1579-1591.
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K.Lu,
X.Yin,
T.Weng,
S.Xi,
L.Li,
G.Xing,
X.Cheng,
X.Yang,
L.Zhang,
and
F.He
(2008).
Targeting WW domains linker of HECT-type ubiquitin ligase Smurf1 for activation by CKIP-1.
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Nat Cell Biol,
10,
994.
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Q.Xi,
W.He,
X.H.Zhang,
H.V.Le,
and
J.Massagué
(2008).
Genome-wide impact of the BRG1 SWI/SNF chromatin remodeler on the transforming growth factor beta transcriptional program.
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J Biol Chem,
283,
1146-1155.
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S.Beaudenon,
and
J.M.Huibregtse
(2008).
HPV E6, E6AP and cervical cancer.
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BMC Biochem,
9,
S4.
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S.Ross,
and
C.S.Hill
(2008).
How the Smads regulate transcription.
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Int J Biochem Cell Biol,
40,
383-408.
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Y.G.Chang,
X.Z.Yan,
Y.Y.Xie,
X.C.Gao,
A.X.Song,
D.E.Zhang,
and
H.Y.Hu
(2008).
Different roles for two ubiquitin-like domains of ISG15 in protein modification.
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J Biol Chem,
283,
13370-13377.
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Y.Inoue,
and
T.Imamura
(2008).
Regulation of TGF-beta family signaling by E3 ubiquitin ligases.
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Cancer Sci,
99,
2107-2112.
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Y.Zhu,
H.Li,
L.Hu,
J.Wang,
Y.Zhou,
Z.Pang,
L.Liu,
and
F.Shao
(2008).
Structure of a Shigella effector reveals a new class of ubiquitin ligases.
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Nat Struct Mol Biol,
15,
1302-1308.
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PDB code:
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B.Schmierer,
and
C.S.Hill
(2007).
TGFbeta-SMAD signal transduction: molecular specificity and functional flexibility.
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Nat Rev Mol Cell Biol,
8,
970-982.
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B.T.Dye,
and
B.A.Schulman
(2007).
Structural mechanisms underlying posttranslational modification by ubiquitin-like proteins.
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Annu Rev Biophys Biomol Struct,
36,
131-150.
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C.Wang,
O.Schueler-Furman,
I.Andre,
N.London,
S.J.Fleishman,
P.Bradley,
B.Qian,
and
D.Baker
(2007).
RosettaDock in CAPRI rounds 6-12.
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Proteins,
69,
758-763.
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G.Terashi,
M.Takeda-Shitaka,
K.Kanou,
M.Iwadate,
D.Takaya,
and
H.Umeyama
(2007).
The SKE-DOCK server and human teams based on a combined method of shape complementarity and free energy estimation.
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Proteins,
69,
866-872.
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H.Li,
Z.Zhang,
B.Wang,
J.Zhang,
Y.Zhao,
and
Y.Jin
(2007).
Wwp2-mediated ubiquitination of the RNA polymerase II large subunit in mouse embryonic pluripotent stem cells.
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Mol Cell Biol,
27,
5296-5305.
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M.Scheffner,
and
O.Staub
(2007).
HECT E3s and human disease.
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BMC Biochem,
8,
S6.
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P.Knipscheer,
and
T.K.Sixma
(2007).
Protein-protein interactions regulate Ubl conjugation.
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| |
Curr Opin Struct Biol,
17,
665-673.
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S.Chaudhury,
A.Sircar,
A.Sivasubramanian,
M.Berrondo,
and
J.J.Gray
(2007).
Incorporating biochemical information and backbone flexibility in RosettaDock for CAPRI rounds 6-12.
|
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Proteins,
69,
793-800.
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S.Itoh,
and
P.ten Dijke
(2007).
Negative regulation of TGF-beta receptor/Smad signal transduction.
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Curr Opin Cell Biol,
19,
176-184.
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S.Qin,
and
H.X.Zhou
(2007).
A holistic approach to protein docking.
|
| |
Proteins,
69,
743-749.
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S.Wiesner,
A.A.Ogunjimi,
H.R.Wang,
D.Rotin,
F.Sicheri,
J.L.Wrana,
and
J.D.Forman-Kay
(2007).
Autoinhibition of the HECT-type ubiquitin ligase Smurf2 through its C2 domain.
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Cell,
130,
651-662.
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PDB code:
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T.Woelk,
S.Sigismund,
L.Penengo,
and
S.Polo
(2007).
The ubiquitination code: a signalling problem.
|
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Cell Div,
2,
11.
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Y.Chen
(2007).
The enzymes in ubiquitin-like post-translational modifications.
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Biosci Trends,
1,
16-25.
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Y.Kee,
and
J.M.Huibregtse
(2007).
Regulation of catalytic activities of HECT ubiquitin ligases.
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Biochem Biophys Res Commun,
354,
329-333.
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Z.M.Eletr,
and
B.Kuhlman
(2007).
Sequence determinants of E2-E6AP binding affinity and specificity.
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J Mol Biol,
369,
419-428.
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Z.Zi,
and
E.Klipp
(2007).
Constraint-based modeling and kinetic analysis of the smad dependent tgf-Beta signaling pathway.
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PLoS ONE,
2,
e936.
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D.C.Jones,
M.N.Wein,
M.Oukka,
J.G.Hofstaetter,
M.J.Glimcher,
and
L.H.Glimcher
(2006).
Regulation of adult bone mass by the zinc finger adapter protein Schnurri-3.
|
| |
Science,
312,
1223-1227.
|
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E.Gallagher,
M.Gao,
Y.C.Liu,
and
M.Karin
(2006).
Activation of the E3 ubiquitin ligase Itch through a phosphorylation-induced conformational change.
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| |
Proc Natl Acad Sci U S A,
103,
1717-1722.
|
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L.Izzi,
and
L.Attisano
(2006).
Ubiquitin-dependent regulation of TGFbeta signaling in cancer.
|
| |
Neoplasia,
8,
677-688.
|
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O.Kerscher,
R.Felberbaum,
and
M.Hochstrasser
(2006).
Modification of proteins by ubiquitin and ubiquitin-like proteins.
|
| |
Annu Rev Cell Dev Biol,
22,
159-180.
|
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P.A.Chong,
H.Lin,
J.L.Wrana,
and
J.D.Forman-Kay
(2006).
An expanded WW domain recognition motif revealed by the interaction between Smad7 and the E3 ubiquitin ligase Smurf2.
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J Biol Chem,
281,
17069-17075.
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PDB code:
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M.Wang,
and
C.M.Pickart
(2005).
Different HECT domain ubiquitin ligases employ distinct mechanisms of polyubiquitin chain synthesis.
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EMBO J,
24,
4324-4333.
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Where a reference describes a PDB structure, the PDB
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