蛋白質(zhì)磷酸酶-2A（protein phosphatae 2A,，PP2A）是真核生物體內(nèi)的主要絲/蘇氨酸蛋白磷酸酶,，在結(jié)構(gòu)上擁有很多不同基因編碼的亞基，并且分別組成多種不同的PP2A全酶,，參與到細(xì)胞周期,、DNA復(fù)制,、信號轉(zhuǎn)導(dǎo)、細(xì)胞分化和細(xì)胞惡性轉(zhuǎn)化等多種細(xì)胞生物學(xué)事件,，并且和神經(jīng)退行性疾病等多種疾病有關(guān),。
PP2A占到大腦蛋白質(zhì)總量的1%。而Tau蛋白是大腦中另一種含量豐富的蛋白,，在高度磷酸化條件下,，Tau蛋白會聚集成為神經(jīng)原纖維纏結(jié)。在2008年9月26日出版的《分子細(xì)胞》（Molecular Cell）上,，來自美國普林斯頓大學(xué)的施一公等科學(xué)家表示,，他們發(fā)現(xiàn)了一種影響Tau蛋白脫磷酸的異源三聚體酶PP2A的結(jié)構(gòu)和作用機制。
蛋白質(zhì)磷酸酶-2A調(diào)節(jié)多種細(xì)胞生理的關(guān)鍵過程,，而B/B55/PR55調(diào)節(jié)家族被認(rèn)為在Tau的脫磷酸過程中起到了關(guān)鍵的作用,，Tau蛋白的高度磷酸化是造成阿茲海默癥的原因之一。在此之前科學(xué)家對于PP2A-Tau之間聯(lián)系的內(nèi)在機制了解的很少,，在本期的封面文章中,，作者表示他們得到了Tau脫磷酸測試的完全重構(gòu)，同時還得到了一種包含調(diào)節(jié)亞基Bα的異源三聚體PP2A全酶,。
結(jié)果表明,，調(diào)節(jié)亞基Bα將顯著的促進磷酸化Tau蛋白的脫磷酸過程。Bα調(diào)節(jié)亞基包含一個七面的β螺旋槳結(jié)構(gòu)（seven-bladed propeller）,，在螺旋槳結(jié)構(gòu)的中央還存在一個酸性的底物結(jié)合凹槽,。β螺旋槳通過一個突出的β發(fā)夾狀結(jié)構(gòu)結(jié)合在PP2A支架亞基上。研究最終揭示出PP2A調(diào)節(jié)的Tau蛋白脫磷酸過程的基礎(chǔ),。（生物谷Bioon.com）
生物谷推薦原始出處：
Molecular Cell,，Vol 31, 873, 26 September 2008，Yanhui Xu, Yigong Shi
Structure of a Protein Phosphatase 2A Holoenzyme: Insights into B55-Mediated Tau Dephosphorylation
Yanhui Xu,1,2,3 Yu Chen,1,2 Ping Zhang,1 Philip D. Jeffrey,1 and Yigong Shi1,4,
1 Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
2 These authors contributed equally to this work
3 Present address: Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China
4 Present address: Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China
Protein phosphatase 2A (PP2A) regulates many essential aspects of cellular physiology. Members of the regulatory B/B55/PR55 family are thought to play a key role in the dephosphorylation of Tau, whose hyperphosphorylation contributes to Alzheimer's disease. The underlying mechanisms of the PP2A-Tau connection remain largely enigmatic. Here, we report the complete reconstitution of a Tau dephosphorylation assay and the crystal structure of a heterotrimeric PP2A holoenzyme involving the regulatory subunit Bα. We show that Bα specifically and markedly facilitates dephosphorylation of the phosphorylated Tau in our reconstituted assay. The Bα subunit comprises a seven-bladed β propeller, with an acidic, substrate-binding groove located in the center of the propeller. The β propeller latches onto the ridge of the PP2A scaffold subunit with the help of a protruding β hairpin arm. Structure-guided mutagenesis studies revealed the underpinnings of PP2A-mediated dephosphorylation of Tau.
