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首页> 外文期刊>Journal of Molecular Biology >The structure of a monomeric mutant Cks protein reveals multiple functions for a conserved hinge-region proline.
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The structure of a monomeric mutant Cks protein reveals multiple functions for a conserved hinge-region proline.

机译：单体突变体Cks蛋白的结构揭示了保守的铰链区脯氨酸的多种功能。

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摘要

Cks (cyclin-dependent kinase subunit) proteins are essential eukaryotic cell cycle regulatory proteins that physically associate with cyclin-dependent kinases (Cdks) to modulate their activity. Cks proteins have also been studied for their ability to form domain-swapped dimers by exchanging beta-strands. Domain swapping is mediated by a conserved beta-hinge region containing two proline residues. Previous structural studies indicate that Cks in its dimer form is unable to bind Cdk, suggesting that the monomer-dimer equilibrium of Cks may have an effect on Cks-mediated Cdk regulation. We present the crystal structure of a proline-to-alanine mutant Saccharomyces cerevisiae Cks protein (Cks1 P93A) that preferentially adopts the monomer conformation but surprisingly fails to bind Cdk. Comparison of the Cks1 P93A structure to that of other Cks proteins reveals that Pro93 is critical for stabilizing a multiple beta-turn structure in the hinge region that properly positions an essential Cdk-binding residue. Additionally, we find that these beta-turn formations, conserved in Cks homologs, have implications for the mechanism and preferentiality of strand exchange. Together, our observations suggest that the conservation of Cks hinge-region prolines reflects their functions in forming a Cdk binding interface and that the ability of these prolines to control partitioning between monomer and dimer is a consequence of the beta-turn networks within the hinge.
机译：Cks（细胞周期蛋白依赖性激酶亚基）蛋白是必不可少的真核细胞周期调节蛋白，可与细胞周期蛋白依赖性激酶（Cdks）物理关联，以调节其活性。还研究了Cks蛋白通过交换β链形成域交换二聚体的能力。域交换由包含两个脯氨酸残基的保守β-铰链区介导。先前的结构研究表明，其二聚体形式的Cks无法结合Cdk，这表明Cks的单体-二聚体平衡可能会对Cks介导的Cdk调节产生影响。我们介绍脯氨酸到丙氨酸突变体酿酒酵母Cks蛋白（Cks1 P93A）的晶体结构，其优先采用单体构象，但出乎意料的是无法结合Cdk。 Cks1 P93A结构与其他Cks蛋白的结构比较表明，Pro93对于稳定铰链区中正确定位必需Cdk结合残基的多重β-转角结构至关重要。此外，我们发现这些在Cks同源物中保守的β-转角形成对链交换的机制和优先级有影响。在一起，我们的观察结果表明，Cks铰链区脯氨酸的保守性反映了它们在形成Cdk结合界面中的功能，并且这些脯氨酸控制单体和二聚体之间分配的能力是铰链内β-转角网络的结果。

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