气候变化领域集成服务门户(CCPortal): Ancient origins of allosteric activation in a Ser-Thr kinase

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DOI	10.1126/science.aay9959
	Ancient origins of allosteric activation in a Ser-Thr kinase
	Hadzipasic A.; Wilson C.; Nguyen V.; Kern N.; Kim C.; Pitsawong W.; Villali J.; Zheng Y.; Kern D.
发表日期	2020
ISSN	0036-8075
起始页码	912
结束页码	917
卷号	367 期号:6480
英文摘要	A myriad of cellular events are regulated by allostery; therefore, evolution of this process is of fundamental interest. Here, we use ancestral sequence reconstruction to resurrect ancestors of two colocalizing proteins, Aurora A kinase and its allosteric activator TPX2 (targeting protein for Xklp2), 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 has remained stable over 1 billion years of evolution. As the microtubule-associated protein TPX2 appeared, efficient kinase binding to TPX2 evolved, likely owing 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. © 2020 American Association for the Advancement of Science. All rights reserved.
关键词	aurora A kinase microtubule associated protein TPX2 protein unclassified drug activation energy ancestry cell chemical binding experimental study fitness protein allosterism amino acid sequence Article binding affinity binding site enzyme activation enzyme activity enzyme binding enzyme localization enzyme phosphorylation gene duplication horizontal gene transfer human hydrophobicity intracellular signaling phylogenetic tree phylogeny priority journal protein binding protein localization protein protein interaction
语种	英语
来源机构	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/133690
推荐引用方式 GB/T 7714	Hadzipasic A.,Wilson C.,Nguyen V.,et al. Ancient origins of allosteric activation in a Ser-Thr kinase[J]. Science,2020,367(6480).
APA	Hadzipasic A..,Wilson C..,Nguyen V..,Kern N..,Kim C..,...&Kern D..(2020).Ancient origins of allosteric activation in a Ser-Thr kinase.,367(6480).
MLA	Hadzipasic A.,et al."Ancient origins of allosteric activation in a Ser-Thr kinase".367.6480(2020).