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PDBsum entry 4ggc
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References listed in PDB file
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Key reference
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Title
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Structural analysis of human cdc20 supports multisite degron recognition by apc/c.
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Authors
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W.Tian,
B.Li,
R.Warrington,
D.R.Tomchick,
H.Yu,
X.Luo.
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Ref.
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Proc Natl Acad Sci U S A, 2012,
109,
18419-18424.
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PubMed id
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Abstract
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The anaphase-promoting complex/cyclosome (APC/C) promotes anaphase onset and
mitotic exit through ubiquitinating securin and cyclin B1. The mitotic APC/C
activator, the cell division cycle 20 (Cdc20) protein, directly interacts with
APC/C degrons--the destruction (D) and KEN boxes. APC/C(Cdc20) is the target of
the spindle checkpoint. Checkpoint inhibition of APC/C(Cdc20) requires the
binding of a BubR1 KEN box to Cdc20. How APC/C recognizes substrates is not
understood. We report the crystal structures of human Cdc20 alone or bound to a
BubR1 KEN box. Cdc20 has a disordered N-terminal region and a C-terminal WD40 β
propeller with a preformed KEN-box-binding site at its top face. We identify a
second conserved surface at the side of the Cdc20 β propeller as a
D-box-binding site. The D box of securin, but not its KEN box, is critical for
securin ubiquitination by APC/C(Cdc20). Although both motifs contribute to
securin ubiquitination by APC/C(Cdh1), securin mutants lacking either motif are
efficiently ubiquitinated. Furthermore, D-box peptides diminish the
ubiquitination of KEN-box substrates by APC/C(Cdh1), suggesting possible
competition between the two motifs. Our results indicate the lack of strong
positive cooperativity between the two degrons of securin. We propose that
low-cooperativity, multisite target recognition enables APC/C to robustly
ubiquitinate diverse substrates and helps to drive cell cycle oscillations.
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Secondary reference #1
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Title
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Cdc20: a wd40 activator for a cell cycle degradation machine.
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Author
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H.Yu.
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Ref.
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Mol Cell, 2007,
27,
3.
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PubMed id
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Secondary reference #2
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Title
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Ken-Box-Dependent degradation of bub1 spindle checkpo kinase by the anaphase-Promoting complex/cyclosome
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Authors
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W.Qi,
H.Yu.
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Ref.
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j biol chem, 2007,
282,
3672.
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Secondary reference #3
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Title
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Mad2-Independent inhibition of apc-Cdc20 by the mitot checkpoint protein bubr1
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Authors
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Z.Tang,
R.Bharadwaj,
B.Li,
H.Yu.
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Ref.
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dev cell, 2001,
1,
227.
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