對 HIV 在人類細胞中的復制來說,， HIV 必須將其單股 RNA 的基因組轉化成為可以整合至宿主基因組中的雙股 DNA ,。這一復雜的過程需要有數種酶的活性，其中包括涉及 DNA 合成,、 RNA- DNA 復制中間產物中 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移使得新合成的 DNA 可以在模版內或模版間移動等酶的活性,。不同尋常的事,，所有這些任務都是由一種單一的酶來進行的： HIV 逆轉錄酶（ RT ）。
在 2008 年 11 月 14 日 《科學》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,。應用 熒光共振能量轉移的方法，該研究團隊對個體 RT 分子與核酸底物之間的相互作用進行了實時的監(jiān)控,。 他們發(fā)現,，這種酶在雙股核酸之間滑行了長距離，并在相反的兩個端點之間進行快速的穿梭行動,。另外,，它還能夠在支持不同酶活性的相反的結合方位之間自動地翻轉。由于 RT 是抗 HIV 療法中的一個主要的標靶,，對這種酶的更深的了解會對未來的藥物設計有所助益,。（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.
