美國(guó)斯克利普斯研究院（TSRI）的研究人員近日揭示了大分子機(jī)器如何解開(kāi)細(xì)胞核內(nèi)長(zhǎng)而糾結(jié)的DNA鏈。這種DNA解旋極為重要,，它能指導(dǎo)合成具有許多特定功能的蛋白,。相關(guān)研究論文在線發(fā)表于11月23日的《自然—結(jié)構(gòu)與分子生物學(xué)》（Nature Structural & Molecular Biology）上。
研究人員使用大分子低溫電子顯微鏡,，記錄了保存于極低溫度下的單個(gè)分子的圖像,，并用這些圖像來(lái)判定分子的結(jié)構(gòu)。研究人員采用啤酒酵母做樣本,，給染色質(zhì)重構(gòu)復(fù)合物RSC——一種大型且靈活的解旋DNA的蛋白機(jī)器——和核小體的聯(lián)合體拍攝了數(shù)千張照片,。之后研究人員使用強(qiáng)大的數(shù)字處理技術(shù),，將單獨(dú)的RSC分子二維圖像轉(zhuǎn)為運(yùn)轉(zhuǎn)中分子的詳細(xì)三維圖像。
RSC是由13種不同蛋白組成的巨大的復(fù)合物,，研究人員首先發(fā)現(xiàn)它具有一個(gè)單個(gè)的核小體,，看起來(lái)像夾鉗。研究人員接著發(fā)現(xiàn),，RCS在DNA中制造了一個(gè)小的突起,，使DNA相對(duì)于組蛋白的遷移成為可能，從而暴露DNA使其可被“閱讀”,。
研究領(lǐng)導(dǎo)者,、斯克利普斯研究院副教授Francisco Asturias說(shuō)：“通過(guò)外部能源（ATP水解），RSC能夠不斷地把DNA從組蛋白中拉出,，最終暴露出全部DNA,。有趣的是，雖然DNA逐漸暴露出來(lái),，但綁定到RSC的核小體卻保持完整,。”
Asturias表示：“每次你的細(xì)胞表達(dá)一個(gè)基因。都會(huì)進(jìn)行這樣的解包和打包過(guò)程,。這一關(guān)鍵過(guò)程每天在我們的每一個(gè)細(xì)胞中發(fā)生無(wú)數(shù)次,，但是我們對(duì)其機(jī)理一直不甚了解。我們揭示的這一結(jié)構(gòu)為理解基因表達(dá)調(diào)控過(guò)程的起始步驟之一提供了線索,。”（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Structural & Molecular Biology,，doi:10.1038/nsmb.1524，Yuriy Chaban,，F(xiàn)rancisco J Asturias
Structure of a RSC–nucleosome complex and insights into chromatin remodeling
Yuriy Chaban1, Chukwudi Ezeokonkwo1, Wen-Hsiang Chung1, Fan Zhang1, Roger D Kornberg2, Barbara Maier-Davis2, Yahli Lorch2 & Francisco J Asturias1
Abstract
ATP-dependent chromatin-remodeling complexes, such as RSC, can reposition, evict or restructure nucleosomes. A structure of a RSC–nucleosome complex with a nucleosome determined by cryo-EM shows the nucleosome bound in a central RSC cavity. Extensive interaction of RSC with histones and DNA seems to destabilize the nucleosome and lead to an overall ATP-independent rearrangement of its structure. Nucleosomal DNA appears disordered and largely free to bulge out into solution as required for remodeling, but the structure of the RSC–nucleosome complex indicates that RSC is unlikely to displace the octamer from the nucleosome to which it is bound. Consideration of the RSC–nucleosome structure and published biochemical information suggests that ATP-dependent DNA translocation by RSC may result in the eviction of histone octamers from adjacent nucleosomes.
1 Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
2 Department of Structural Biology, Stanford University Medical Center, Stanford, California 94035, USA.
