延伸體(elongator)是一個多蛋白復(fù)合物,,由Elp1-3及Elp4-6兩種亞復(fù)合體組成,。研究表明,,延伸體在酵母和人類中是高度保守的,,它在RNA聚合酶II介導(dǎo)的轉(zhuǎn)錄延伸及其它許多過程(比如細胞骨架構(gòu)建,、胞外分泌以及tRNA修飾)中起到了重要作用,。
2012年2月,來自EMBL和IGBMC的科學(xué)家研究了延伸體蛋白中的三種蛋白,,即Elp4,,Elp5和Elp6,他們已經(jīng)發(fā)現(xiàn)這三種蛋白不只是簡單地堆積在一起產(chǎn)生三蛋白組(trio),,而且兩種相同的三蛋白組發(fā)生聯(lián)合形成一種環(huán),。詳見:Nature子刊:延伸體復(fù)合物環(huán)狀結(jié)構(gòu)有助確保蛋白準(zhǔn)確產(chǎn)生。
近日,,來自南開大學(xué)龍加福教授的課題組確定了酵母Elp4-6亞復(fù)合體的晶體結(jié)構(gòu),闡明了延伸體復(fù)合物的裝配及其底物識別機制,。相關(guān)論文發(fā)表在5月2日的The Journal of Biological Chemistry。
分析Elp4-6的晶體結(jié)構(gòu)得知,,Elp6作為了一個“橋”來連接Elp4和Elp5,。詳盡的結(jié)構(gòu)及序列分析表明,Elp4-6亞復(fù)合體的每一個亞基都形成了一個RecA-ATPase樣的折疊,,但是這些結(jié)構(gòu)沒有ATPases的核心序列特征,。
定點突變及生化分析表明,Elp4-6亞復(fù)合體能夠在體外及體內(nèi)形成六聚體環(huán)狀結(jié)構(gòu),。
此外,,GST pull-down分析顯示,Elp4-6的環(huán)狀結(jié)構(gòu)對于它特異性的與組蛋白H3的結(jié)合是非常重要的,。(生物谷Deepblue編譯)
doi: 10.1074/jbc.M112.341560
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Crystal structure of the elongator subcomplex Elp4-6
Zhijie Lin, Weijing Zhao, Wentao Diao, Xingqiao Xie, Zheng Wang, Jinxiu Zhang, Yuequan Shen and Jiafu Long.
Elongator is a multiprotein complex composed of two subcomplexes, Elp1-3 and Elp4-6. Elongator is highly conserved between yeast and humans and plays an important role in RNA polymerase II-mediated transcriptional elongation and many other processes, including cytoskeleton organization, exocytosis, and tRNA modification.Here, we determined the crystal structure of the Elp4-6 subcomplex of yeast. The overall structure of Elp4-6 revealed that Elp6 acts as a bridge to assemble Elp4 and Elp5.Detailed structural and sequence analyses revealed that each subunit in the Elp4-6 subcomplex forms a RecA-ATPase-like fold although it lacks the key sequence signature of ATPases.Site-directed mutagenesis and biochemical analyses indicated that the Elp4-6 subcomplex can assemble into a hexameric ring-shaped structure in vitro and in vivo.Furthermore, GST pull-down assays showed that the ring-shaped assembly of the Elp4-6 subcomplex is important for its specific histone H3 binding. Our results may shed light on the substrate recognition and assembly of the holo-Elongator complex.