對 HIV 在人類細(xì)胞中的復(fù)制來說,， HIV 必須將其單股 RNA 的基因組轉(zhuǎn)化成為可以整合至宿主基因組中的雙股 DNA ,。這一復(fù)雜的過程需要有數(shù)種酶的活性，其中包括涉及 DNA 合成,、 RNA- DNA 復(fù)制中間產(chǎn)物中 RNA 鏈的降解,、核酸鏈的置換以移除剩下的 RNA 及 DNA 片斷，使得第 2 條 DNA 鏈得以合成以及核酸鏈的轉(zhuǎn)移使得新合成的 DNA 可以在模版內(nèi)或模版間移動(dòng)等酶的活性,。不同尋常的事,，所有這些任務(wù)都是由一種單一的酶來進(jìn)行的： HIV 逆轉(zhuǎn)錄酶（ RT ）。
在 2008 年 11 月 14 日 《科學(xué)》雜志的一篇 Report 中,， Liu 等人為人們就 RT 是如何在其多種功能之間變換的提供了新的見解,。應(yīng)用 熒光共振能量轉(zhuǎn)移的方法，該研究團(tuán)隊(duì)對個(gè)體 RT 分子與核酸底物之間的相互作用進(jìn)行了實(shí)時(shí)的監(jiān)控,。 他們發(fā)現(xiàn),，這種酶在雙股核酸之間滑行了長距離，并在相反的兩個(gè)端點(diǎn)之間進(jìn)行快速的穿梭行動(dòng),。另外,，它還能夠在支持不同酶活性的相反的結(jié)合方位之間自動(dòng)地翻轉(zhuǎn)。由于 RT 是抗 HIV 療法中的一個(gè)主要的標(biāo)靶,，對這種酶的更深的了解會(huì)對未來的藥物設(shè)計(jì)有所助益,。（生物谷Bioon.com）
生物谷推薦原始出處：
Science 14 November 2008: DOI: 10.1126/science.1163108
Slide into Action: Dynamic Shuttling of HIV Reverse Transcriptase on Nucleic Acid Substrates
Shixin Liu,1 Elio A. Abbondanzieri,1 Jason W. Rausch,4 Stuart F. J. Le Grice,4 Xiaowei Zhuang1,2,3*
The reverse transcriptase (RT) of human immunodeficiency virus (HIV) catalyzes a series of reactions to convert single-stranded viral RNA into double-stranded DNA for host cell integration. This process requires a variety of enzymatic activities, including DNA polymerization, RNA cleavage, strand transfer, and strand displacement synthesis. We used single-molecule fluorescence resonance energy transfer to probe the interactions between RT and nucleic acid substrates in real time. RT was observed to slide on nucleic acid duplexes, rapidly shuttling between opposite termini of the duplex. Upon reaching the DNA 3' terminus, RT can spontaneously flip into a polymerization orientation. Sliding kinetics were regulated by cognate nucleotides and anti-HIV drugs, which stabilized and destabilized the polymerization mode, respectively. These long-range translocation activities facilitate multiple stages of the reverse transcription pathway, including normal DNA polymerization and strand displacement synthesis.
1 Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
2 Department of Physics, Harvard University, Cambridge, MA 02138, USA.
3 Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA.
4 HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702, USA.
