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DOI | 10.1038/nature25745 |
Architecture of an HIV-1 reverse transcriptase initiation complex | |
Larsen, Kevin P.1,2; Mathiharan, Yamuna Kalyani3; Kappel, Kalli1; Coey, Aaron T.1,2; Chen, Dong-Hua2; Barrero, Daniel2; Madigan, Lauren2; Puglisi, Joseph D.2; Skiniotis, Georgios2,3; Puglisi, Elisabetta Viani2 | |
2018-05-03 | |
发表期刊 | NATURE |
ISSN | 0028-0836 |
EISSN | 1476-4687 |
出版年 | 2018 |
卷号 | 557期号:7703页码:118-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Reverse transcription of the HIV-1 RNA genome into doublestranded DNA is a central step in viral infection1 and a common target of antiretroviral drugs(2). The reaction is catalysed by viral reverse transcriptase (RT)(3,4) that is packaged in an infectious virion with two copies of viral genomic RNA(5) each bound to host lysine 3 transfer RNA (tRNA(3)(Lys)), which acts as a primer for initiation of reverse transcription(6,7). Upon viral entry into cells, initiation is slow and non-processive compared to elongation(8,9). Despite extensive efforts, the structural basis of RT function during initiation has remained a mystery. Here we use cryo-electron microscopy to determine a three-dimensional structure of an HIV-1 RT initiation complex. In our structure, RT is in an inactive polymerase conformation with open fingers and thumb and with the nucleic acid primer-template complex shifted away from the active site. The primer binding site (PBS) helix formed between tRNA(3)(Lys) and HIV-1 RNA lies in the cleft of RT and is extended by additional pairing interactions. The 5' end of the tRNA refolds and stacks on the PBS to create a long helical structure, while the remaining viral RNA forms two helical stems positioned above the RT active site, with a linker that connects these helices to the RNase H region of the PBS. Our results illustrate how RNA structure in the initiation complex alters RT conformation to decrease activity, highlighting a potential target for drug action. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000431234500041 |
WOS关键词 | PRIMER ACTIVATION SIGNAL ; DEPENDENT DNA-POLYMERASE ; SECONDARY STRUCTURE ; RNA SEQUENCES ; VIRUS ; ELONGATION ; DYNAMICS ; SYSTEM ; TRNA(3)(LYS) ; RESOLUTION |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/202857 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Stanford Univ, Program Biophys, Stanford, CA 94305 USA; 2.Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA; 3.Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA USA |
推荐引用方式 GB/T 7714 | Larsen, Kevin P.,Mathiharan, Yamuna Kalyani,Kappel, Kalli,et al. Architecture of an HIV-1 reverse transcriptase initiation complex[J]. NATURE,2018,557(7703):118-+. |
APA | Larsen, Kevin P..,Mathiharan, Yamuna Kalyani.,Kappel, Kalli.,Coey, Aaron T..,Chen, Dong-Hua.,...&Puglisi, Elisabetta Viani.(2018).Architecture of an HIV-1 reverse transcriptase initiation complex.NATURE,557(7703),118-+. |
MLA | Larsen, Kevin P.,et al."Architecture of an HIV-1 reverse transcriptase initiation complex".NATURE 557.7703(2018):118-+. |
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