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Initiation complex dynamics direct the transitions between distinct phases of early HIV reverse transcription

  1. Author:
    Liu, S. X.
    Harada, B. T.
    Miller, J. T.
    Le Grice, S. F. J.
    Zhuang, X. W.

  2. Author Address

    [Liu, Shixin; Zhuang, Xiaowei] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Harada, Bryan T.] Harvard Univ, Grad Program Biophys, Cambridge, MA 02138 USA. [Miller, Jennifer T.; Le Grice, Stuart F. J.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. [Zhuang, Xiaowei] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. [Zhuang, Xiaowei] Howard Hughes Med Inst, Cambridge, MA USA.;Zhuang, XW, Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.;zhuang@chemistry.harvard.edu
    1. Year: 2010
    2. Date: Dec
  2. Journal: Nature Structural & Molecular Biology
    1. 17
    2. 12
    3. Pages: 1453-U83
  4. Type of Article: Article
  5. ISSN: 1545-9985
  1. Abstract:

    Human immunodeficiency virus (HIV) initiates reverse transcription of its viral RNA (vRNA) genome from a cellular tRNA(3)(Lys) primer. This process is characterized by a slow initiation phase with specific pauses, followed by a fast elongation phase. We report a single-molecule study that monitors the dynamics of individual initiation complexes, comprised of vRNA, tRNA and HIV reverse transcriptase (RT). RT transitions between two opposite binding orientations on tRNA-vRNA complexes, and the prominent pausing events are related to RT binding in a flipped orientation opposite to the polymerization-competent configuration. A stem-loop structure within the vRNA is responsible for maintaining the enzyme predominantly in this flipped orientation. Disruption of the stem-loop structure triggers the initiation-to-elongation transition. These results highlight the important role of the structural dynamics of the initiation complex in directing transitions between early reverse transcription phases. (C) 2010 Nature America, Inc. All rights reserved.

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  2. DOI: 10.1038/nsmb.1937
  3. View record in Web of Science®
  4. WOS: 000284942200009

Library Notes

  1. Fiscal Year: FY2010-2011
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