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PDBsum entry 3eb5
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References listed in PDB file
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Key reference
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Title
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Structures of the ciap2 ring domain reveal conformational changes associated with ubiquitin-Conjugating enzyme (e2) recruitment.
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Authors
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P.D.Mace,
K.Linke,
R.Feltham,
F.R.Schumacher,
C.A.Smith,
D.L.Vaux,
J.Silke,
C.L.Day.
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Ref.
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J Biol Chem, 2008,
283,
31633-31640.
[DOI no: ]
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PubMed id
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Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
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Abstract
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Inhibitor of apoptosis (IAP) proteins are key negative regulators of cell death
that are highly expressed in many cancers. Cell death caused by antagonists that
bind to IAP proteins is associated with their ubiquitylation and degradation.
The RING domain at the C terminus of IAP proteins is pivotal. Here we report the
crystal structures of the cIAP2 RING domain homodimer alone, and bound to the
ubiquitin-conjugating (E2) enzyme UbcH5b. These structures show that small
changes in the RING domain accompany E2 binding. By mutating residues at the
E2-binding surface, we show that autoubiquitylation is required for regulation
of IAP abundance. Dimer formation is also critical, and mutation of a single
C-terminal residue abrogated dimer formation and E3 ligase activity was
diminished. We further demonstrate that disruption of E2 binding, or
dimerization, stabilizes IAP proteins against IAP antagonists in vivo.
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Figure 3.
A symmetric complex is formed between cIAP2 RING dimers and
UbcH5b. A, schematic representation of the crystal structure of
cIAP2 RING domain (bright green) bound to UbcH5b (brown). The
complex is symmetrical around the RING domain dimer interface,
with one RING and one UbcH5b per asymmetric unit. B, comparison
of the cIAP2 RING domain dimer (light green) with the cIAP2
RING-dimer from the complex structure (bright green). The RING
domains were overlaid using secondary structure matching. C,
close up view of the C terminus from free and E2-bound cIAP2
RING.
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Figure 5.
Conserved features in RING domains mediate E2 recruitment.
The surfaces of c-Cbl, cIAP2, and CHIP that interact with the E2
are colored according to electrostatic potential, and homologous
regions are indicated in blue, yellow, and red. Residues that
contribute to the additional interaction interfaces are
highlighted in black.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2008,
283,
31633-31640)
copyright 2008.
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