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PDBsum entry 2ass
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Cell cycle/ligase/protein turnover
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PDB id
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2ass
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Contents |
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143 a.a.
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325 a.a.
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69 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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Structural basis of the cks1-Dependent recognition of p27(kip1) by the scf(skp2) ubiquitin ligase.
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Authors
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B.Hao,
N.Zheng,
B.A.Schulman,
G.Wu,
J.J.Miller,
M.Pagano,
N.P.Pavletich.
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Ref.
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Mol Cell, 2005,
20,
9.
[DOI no: ]
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PubMed id
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Abstract
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The ubiquitin-mediated proteolysis of the Cdk2 inhibitor p27(Kip1) plays a
central role in cell cycle progression, and enhanced degradation of p27(Kip1) is
associated with many common cancers. Proteolysis of p27(Kip1) is triggered by
Thr187 phosphorylation, which leads to the binding of the SCF(Skp2)
(Skp1-Cul1-Rbx1-Skp2) ubiquitin ligase complex. Unlike other known SCF
substrates, p27(Kip1) ubiquitination also requires the accessory protein Cks1.
The crystal structure of the Skp1-Skp2-Cks1 complex bound to a p27(Kip1)
phosphopeptide shows that Cks1 binds to the leucine-rich repeat (LRR) domain and
C-terminal tail of Skp2, whereas p27(Kip1) binds to both Cks1 and Skp2. The
phosphorylated Thr187 side chain of p27(Kip1) is recognized by a Cks1 phosphate
binding site, whereas the side chain of an invariant Glu185 inserts into the
interface between Skp2 and Cks1, interacting with both. The structure and
biochemical data support the proposed model that Cdk2-cyclin A contributes to
the recruitment of p27(Kip1) to the SCF(Skp2)-Cks1 complex.
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Figure 2.
Figure 2. Structure of the Skp1-Skp2-Cks1-p27^Kip1 Complex
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Figure 3.
Figure 3. Intermolecular Contacts in the
Skp1-Skp2-Cks1-p27^Kip1 Complex
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The above figures are
reprinted
by permission from Cell Press:
Mol Cell
(2005,
20,
9-0)
copyright 2005.
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