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PDBsum entry 4p5o
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327 a.a.
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75 a.a.
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197 a.a.
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169 a.a.
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76 a.a.
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References listed in PDB file
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Key reference
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Title
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Structure of a ring e3 trapped in action reveals ligation mechanism for the ubiquitin-Like protein nedd8.
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Authors
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D.C.Scott,
V.O.Sviderskiy,
J.K.Monda,
J.R.Lydeard,
S.E.Cho,
J.W.Harper,
B.A.Schulman.
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Ref.
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Cell, 2014,
157,
1671-1684.
[DOI no: ]
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PubMed id
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Abstract
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Most E3 ligases use a RING domain to activate a thioester-linked
E2∼ubiquitin-like protein (UBL) intermediate and promote UBL transfer to a
remotely bound target protein. Nonetheless, RING E3 mechanisms matching a
specific UBL and acceptor lysine remain elusive, including for RBX1, which
mediates NEDD8 ligation to cullins and >10% of all ubiquitination.
We report the structure of a trapped RING E3-E2∼UBL-target intermediate
representing RBX1-UBC12∼NEDD8-CUL1-DCN1, which reveals the mechanism of NEDD8
ligation and how a particular UBL and acceptor lysine are matched by a
multifunctional RING E3. Numerous mechanisms specify cullin neddylation while
preventing noncognate ubiquitin ligation. Notably, E2-E3-target and
RING-E2∼UBL modules are not optimized to function independently, but instead
require integration by the UBL and target for maximal reactivity. The UBL and
target regulate the catalytic machinery by positioning the RING-E2∼UBL
catalytic center, licensing the acceptor lysine, and influencing E2 reactivity,
thereby driving their specific coupling by a multifunctional RING E3.
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