2ass: Difference between revisions

Revision as of 17:30, 21 February 2008

Crystal structure of the Skp1-Skp2-Cks1 complex

OverviewOverview

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.

About this StructureAbout this Structure

2ASS is a Protein complex structure of sequences from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.

ReferenceReference

Structural basis of the Cks1-dependent recognition of p27(Kip1) by the SCF(Skp2) ubiquitin ligase., Hao B, Zheng N, Schulman BA, Wu G, Miller JJ, Pagano M, Pavletich NP, Mol Cell. 2005 Oct 7;20(1):9-19. PMID:16209941

Page seeded by OCA on Thu Feb 21 16:30:39 2008

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OCA

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-<applet load="2ass" size="450" color="white" frame="true" align="right" spinBox="true"
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 '''Crystal structure of the Skp1-Skp2-Cks1 complex'''<br />
 ==Overview==
-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.
+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.
 ==About this Structure==
-ASS is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with PO4 and BEN as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2ASS OCA].
+ASS is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=PO4:'>PO4</scene> and <scene name='pdbligand=BEN:'>BEN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ASS OCA].
 ==Reference==
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 [[Category: Hao, B.]]
 [[Category: Pagano, M.]]
-[[Category: Pavletich, N.P.]]
+[[Category: Pavletich, N P.]]
-[[Category: Schulman, B.A.]]
+[[Category: Schulman, B A.]]
 [[Category: Wu, G.]]
 [[Category: Zhang, N.]]
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 [[Category: scf]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:54:23 2007''
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