Crystal structure and mutational analysis the human CDK2 kinase complex with cell cycle-regulatory protein CksHs1
Crystal structure and mutational analysis the human CDK2 kinase complex with cell cycle-regulatory protein CksHs1
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DOI：
10.1016/s0092-8674(00)81065-x
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发表时间：
1996-03-22
期刊：
影响因子：
64.5
通讯作者：
Tainer, JA
中科院分区：
文献类型：
--
作者：
Bourne, Y;Watson, MH;Tainer, JA
人细胞周期蛋白依赖性激酶2（CDK 2）与CksHs 1（一种必需的酵母细胞周期调节蛋白suc 1和Cks 1的人类同源物）复合的2.6埃晶体结构表明，CksHs 1通过所有四条β链与激酶C-长袍结合。基于突变分析，该界面在生物学上是关键的，但远离CDK 2 N-末端叶、细胞周期蛋白和调节磷酸化位点。CDK 2结合Cks单结构域构象，并与保守的疏水残基加上His-60和Glu-63以其封闭的β-铰链基序构象相互作用。β铰链打开以形成Cks β-互换的二聚体在空间上排除了CDK 2结合，提供了调节CDK 2-Cks相互作用的可能机制。该复合物的一面暴露了Cks上序列保守的磷酸结合区和CDK 2上的ATP结合位点，表明Cks可能在细胞周期中将CDK 2靶向其他磷蛋白。
The 2.6 Angstrom crystal structure for human cyclin-dependent kinase 2 (CDK2) in complex with CksHs1, a human homolog of essential yeast cell cycle-regulatory proteins suc1 and Cks1, reveals that CksHs1 binds via all four beta strands to the kinase C-terminal robe. This interface is biologically critical, based upon mutational analysis, but far from the CDK2 N-terminal lobe, cyclin, and regulatory phosphorylation sites. CDK2 binds the Cks single domain conformation and interacts with conserved hydrophobic residues plus His-60 and Glu-63 in their closed beta-hinge motif conformation. The beta hinge opening to form the Cks beta-interchanged dimer sterically precludes CDK2 binding, providing a possible mechanism regulating CDK2-Cks interactions. One face of the complex exposes the sequence-conserved phosphate-binding region on Cks and the ATP-binding site on CDK2, suggesting that Cks may target CDK2 to other phosphoproteins during the cell cycle.