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PDBsum entry 5jg6
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References listed in PDB file
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Key reference
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Title
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Dual ring e3 architectures regulate multiubiquitination and ubiquitin chain elongation by apc/c.
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Authors
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N.G.Brown,
R.Vanderlinden,
E.R.Watson,
F.Weissmann,
A.Ordureau,
K.P.Wu,
W.Zhang,
S.Yu,
P.Y.Mercredi,
J.S.Harrison,
I.F.Davidson,
R.Qiao,
Y.Lu,
P.Dube,
M.R.Brunner,
C.R.Grace,
D.J.Miller,
D.Haselbach,
M.A.Jarvis,
M.Yamaguchi,
D.Yanishevski,
G.Petzold,
S.S.Sidhu,
B.Kuhlman,
M.W.Kirschner,
J.W.Harper,
J.M.Peters,
H.Stark,
B.A.Schulman.
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Ref.
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Cell, 2016,
165,
1440-1453.
[DOI no: ]
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PubMed id
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Abstract
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Protein ubiquitination involves E1, E2, and E3 trienzyme cascades. E2 and RING
E3 enzymes often collaborate to first prime a substrate with a single ubiquitin
(UB) and then achieve different forms of polyubiquitination: multiubiquitination
of several sites and elongation of linkage-specific UB chains. Here, cryo-EM and
biochemistry show that the human E3 anaphase-promoting complex/cyclosome (APC/C)
and its two partner E2s, UBE2C (aka UBCH10) and UBE2S, adopt specialized
catalytic architectures for these two distinct forms of polyubiquitination. The
APC/C RING constrains UBE2C proximal to a substrate and simultaneously binds a
substrate-linked UB to drive processive multiubiquitination. Alternatively,
during UB chain elongation, the RING does not bind UBE2S but rather lures an
evolving substrate-linked UB to UBE2S positioned through a cullin interaction to
generate a Lys11-linked chain. Our findings define mechanisms of APC/C
regulation, and establish principles by which specialized E3-E2-substrate-UB
architectures control different forms of polyubiquitination.
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