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

Virology
Tiyun WuJ G Levin

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.

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Citations

Oct 29, 2013·Nucleic Acids Research·Mithun MitraJudith G Levin
Nov 26, 2010·Nature Structural & Molecular Biology·Shixin LiuXiaowei Zhuang
Dec 3, 2010·Journal of Virology·Christopher P JonesKarin Musier-Forsyth
Aug 26, 2015·Viruses·Erik D OlsonKarin Musier-Forsyth
May 10, 2011·Trends in Biochemical Sciences·Alan ReinKarin Musier-Forsyth
Mar 19, 2016·Retrovirology·Katarzyna Pachulska-WieczorekKatarzyna J Purzycka
Jun 8, 2014·Virus Research·Jean-Luc DarlixYves Mély
Dec 26, 2012·Trends in Microbiology·Neil M Bell, Andrew M L Lever
Sep 15, 2016·Viruses·Elodie MaillerRedmond P Smyth
Nov 15, 2016·RNA Biology·Serena BernacchiJean-Christophe Paillart
Aug 18, 2017·Journal of Virology·Alice A DuchonKarin Musier-Forsyth
Dec 17, 2010·RNA Biology·Judith G LevinKarin Musier-Forsyth
Aug 5, 2020·Antimicrobial Agents and Chemotherapy·Moisés A ÁrquezLuis Menéndez-Arias
May 22, 2020·ACS Medicinal Chemistry Letters·Stefano CiacoYves Mély

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