Ancient origins of allosteric activation in a Ser-Thr kinase.
Ancient origins of allosteric activation in a Ser-Thr kinase.
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DOI：
10.1126/science.aay9959
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发表时间：
2020-02-21
期刊：
影响因子：
56.9
通讯作者：
Kern, Dorothee
中科院分区：
文献类型：
--
作者：
Hadzipasic, Adelajda;Wilson, Christopher;Vy Nguyen;Kern, Nadja;Kim, Chansik;Pitsawong, Warintra;Villali, Janice;Zheng, Yuejiao;Kern, Dorothee
尽管有无数的细胞事件受到变构的调节，但这一过程的进化在很大程度上是未探索的领域。在这里，我们使用祖先序列重建（ASR）复活的祖先的两个共定位蛋白，极光A激酶和它的变构激活剂TPX 2，实验表征的进化路径的变构激活。活化环的自磷酸化是最古老的活化机制;它在最古老的激酶祖先中充分发展，并在十亿年的进化中保持稳定。随着微管相关蛋白TPX 2的出现，与TPX 2的有效激酶结合可能是由于共定位增加了适应性。随后，TPX 2介导的变构激酶调节逐渐发展。令人惊讶的是，这种调节的进化是在激酶中编码的，并且不是由共同进化的主导机制引起的。通过Aurora激酶及其激活伴侣TPX 2的祖先序列重建研究变构调节的进化。
Despite a myriad of cellular events being regulated by allostery, evolution of this process is largely unexplored territory. Here, we use Ancestral Sequence Reconstruction (ASR) to resurrect ancestors of two colocalizing proteins, Aurora A kinase and its allosteric activator TPX2, to experimentally characterize the evolutionary path of allosteric activation. Autophosphorylation of the activation loop is the most ancient activation mechanism; it is fully developed in the oldest kinase ancestor and remains stable over one billion years of evolution. As the microtubule-associated protein TPX2 appeared, efficient kinase binding to TPX2 evolved likely due to increased fitness by virtue of colocalization. Subsequently, TPX2-mediated allosteric kinase regulation gradually evolved. Surprisingly, evolution of this regulation is encoded in the kinase and did not arise by a dominating mechanism of coevolution. Evolution of allosteric regulation is studied by Ancestral Sequence Reconstruction of Aurora kinase together with its activation partner TPX2.
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人类TPX2是将极光-A激酶靶向纺锤体所必需的。
影响因子：
7.8
作者：
Kufer, Thomas A;Sillje, Herman H W;Korner, Roman;Gruss, Oliver J;Meraldi, Patrick;Nigg, Erich A
通讯作者：
Nigg, Erich A
影响因子：
10.7
作者：
Hedges SB;Marin J;Suleski M;Paymer M;Kumar S
通讯作者：
Kumar S
DOI：
10.1073/pnas.0901522106
发表时间：
2009-06-16
影响因子：
11.1
作者：
Bloom, Jesse D.;Arnold, Frances H.
通讯作者：
Arnold, Frances H.
影响因子：
10.7
作者：
Hanson-Smith V;Kolaczkowski B;Thornton JW
通讯作者：
Thornton JW
影响因子：
64.5
作者：
Coyle SM;Flores J;Lim WA
通讯作者：
Lim WA