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Fundamental differences between the nucleic acid chaperone activities of HIV-1 nucleocapsid protein and Gag or Gag-derived proteins: Biological implications

  1. Author:
    Wu, T. Y.
    Datta, S. A. K.
    Mitra, M.
    Gorelick, R. J.
    Rein, A.
    Levin, J. G.

  2. Author Address

    [Wu, Tiyun; Mitra, Mithun; Levin, Judith G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Genet Lab, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. [Datta, Siddhartha A. K.; Rein, Alan] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Gorelick, Robert J.] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21702 USA.;Levin, JG, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Genet Lab, Program Genom Differentiat, NIH, Bldg 6B,Room 216,6 Ctr Dr, Bethesda, MD 20892 USA.;levinju@mail.nih.gov
    1. Year: 2010
    2. Date: Sep
  2. Journal: Virology
    1. 405
    2. 2
    3. Pages: 556-567
  4. Type of Article: Article
  5. ISSN: 0042-6822
  1. Abstract:

    The HIV-1 Gag polyprotein precursor has multiple domains including nucleocapsid (NC). Although mature NC and NC embedded in Gag are nucleic acid chaperones (proteins that remodel nucleic acid structure), few studies include detailed analysis of the chaperone activity of partially processed Gag proteins and comparison with NC and Gag. Here we address this issue by using a reconstituted minus-strand transfer system. NC and NC-containing Gag proteins exhibited annealing and duplex destabilizing activities required for strand transfer. Surprisingly, unlike NC, with increasing concentrations. Gag proteins drastically inhibited the DNA elongation step. This result is consistent with "nucleic acid-driven multimerization" of Gag and the reported slow dissociation of Gag from bound nucleic acid, which prevent reverse transcriptase from traversing the template ("roadblock" mechanism). Our findings illustrate one reason why NC (and not Gag) has evolved as a critical cofactor in reverse transcription, a paradigm that might also extend to other retrovirus systems. Published by Elsevier Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.virol.2010.06.042
  3. View record in Web of Science®
  4. WOS: 000281130500032

Library Notes

  1. Fiscal Year: FY2009-2010
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