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PDBsum entry 2wx0
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Protein binding
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PDB id
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2wx0
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References listed in PDB file
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Key reference
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Title
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Two-Sided ubiquitin binding explains specificity of the tab2 nzf domain.
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Authors
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Y.Kulathu,
M.Akutsu,
A.Bremm,
K.Hofmann,
D.Komander.
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Ref.
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Nat Struct Biol, 2009,
16,
1328-1330.
[DOI no: ]
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PubMed id
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Abstract
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The protein kinase TAK1 is activated by binding to Lys63 (K63)-linked ubiquitin
chains through its subunit TAB2. Here we analyze crystal structures of the TAB2
NZF domain bound to Lys63-linked di- and triubiquitin, revealing that TAB2 binds
adjacent ubiquitin moieties via two distinct binding sites. The conformational
constraints imposed by TAB2 on a Lys63 dimer cannot be adopted by linear chains,
explaining why TAK1 cannot be activated by linear ubiquitination events.
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Figure 1.
(a) Structure of TAB2 (red, zinc as yellow sphere coordinated
by orange cysteine residues) bound to diubiquitin (green, distal
Ub; cyan, proximal Ub). Ile44, Val70 and Leu8 are shown as blue
sticks. 2|F[0]| – |F[c]| electron density at 1  covers
Gly75, Gly76 and Lys63. (b) Selected residues of TAB2
interacting with ubiquitin are shown in orange. Dotted lines
indicate hydrogen bonds. (c) Arrangement of diubiquitin
complexes in the crystallographic lattice; two asymmetric units
are shown. A dotted line indicates where the continuous chain
can form. A schematic illustrates how the triubiquitin complex
is arranged in the crystal lattice.
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Figure 3.
(a) Binding of TAB2 NZF to Lys63-linked and linear (Lin) di-
and tetraubiquitin. (b) Close-up of the Lys63 linkage showing
the position of Met1 at 10.8 Å distance. (c) Binding of
TAB2 NZF to Lys63- and Lys48-linked di- and tetraubiquitin. (d)
Comparison of TAB2–Lys63-diubiquitin and hHR23A
UBA2–Lys48-diubiquitin (PDB 1ZO6 (ref. 8)). (e) Superposition
of the distal ubiquitin moieties (dark green) from d, with TAB2
shown. Because of the flexible isopeptide linker, the proximal
ubiquitin of Lys48-diubiquitin (light green) can rotate to adopt
a similar conformation as Lys63-diubiquitin on TAB2 (see also
Supplementary Fig. 6).
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2009,
16,
1328-1330)
copyright 2009.
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