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PDBsum entry 1k2f
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Ligase, protein binding
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PDB id
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1k2f
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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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Siah ubiquitin ligase is structurally related to traf and modulates tnf-Alpha signaling.
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Authors
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G.Polekhina,
C.M.House,
N.Traficante,
J.P.Mackay,
F.Relaix,
D.A.Sassoon,
M.W.Parker,
D.D.Bowtell.
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Ref.
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Nat Struct Biol, 2002,
9,
68-75.
[DOI no: ]
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PubMed id
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Abstract
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Members of the Siah (seven in absentia homolog) family of RING domain proteins
are components of E3 ubiquitin ligase complexes that catalyze ubiquitination of
proteins. We have determined the crystal structure of the substrate-binding
domain (SBD) of murine Siah1a to 2.6 A resolution. The structure reveals that
Siah is a dimeric protein and that the SBD adopts an eight-stranded
beta-sandwich fold that is highly similar to the TRAF-C region of TRAF
(TNF-receptor associated factor) proteins. The TRAF-C region interacts with
TNF-alpha receptors and TNF-receptor associated death-domain (TRADD) proteins;
however, our findings indicate that these interactions are unlikely to be
mimicked by Siah. The Siah structure also reveals two novel zinc fingers in a
region with sequence similarity to TRAF. We find that the Siah1a SBD potentiates
TNF-alpha-mediated NF-kappa B activation. Therefore, Siah proteins share
important similarities with the TRAF family of proteins, including their overall
domain architecture, three-dimensional structure and functional activity.
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Figure 4.
Figure 4. Similarities between Siah and TRAF. a, Comparison
of the domain architecture of Siah and TRAF2 proteins. Pink
circle represents the RING domain; blue bar, zinc finger; red
rod, coiled-coil; and green rod, TRAF-C domain. b, Siah1a SBD
stimulation of an NF-  B
reporter assay in 293 cells. Cells were transfected with Siah1a,
Siah1a SBD, TRAF2 or TNF-  and
combinations of TNF- -Siah1a
and TNF- -Siah1a
SBD. Cotransfection of the I B
super repressor was able to reduce NF- B
activation to background levels for all points measured (data
not shown).
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Figure 5.
Figure 5. Surface features of Siah SBD. a, Surface of Siah1a
SBD dimer with the zinc fingers shown in blue and the C-terminal
domains in green. Areas of strictly conserved residues are shown
in red. b,c, Views of SBD after successive 90° rotations along
the long axis of the molecule. A putative RING interacting
region (see text) is indicated by the arrows in (a,c). A star in
(b) highlights a potential binding partner/substrate site (see
text). Images were generated by GRASP60.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2002,
9,
68-75)
copyright 2002.
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Secondary reference #1
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Title
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Isolation and characterisation of murine homologues of the drosophila seven inabsentia gene (sina)
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Authors
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N.G.Della,
P.V.Senior,
D.D.Bowtell.
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Ref.
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development (cambridge), 1993,
117,
1333.
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