Unfolding of DNA quadruplexes induced by HIV-1 nucleocapsid protein

Besik I. Kankia, George Barany, Karin Musier-Forsyth

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The human immunodeficiency virus type 1 nucleocapsid protein (NC) is a nucleic acid chaperone that catalyzes the rearrangement of nucleic acids into their thermodynamically most stable structures. In the present study, a combination of optical and thermodynamic techniques were used to characterize the influence of NC on the secondary structure, thermal stability and energetics of monomolecular DNA quadruplexes formed by the sequence d(GGTTGGTGTGGTTGG) in the presence of K+ or Sr2+. Circular dichroism studies demonstrate that NC effectively unfolds the quadruplexes. Studies carried out with NC variants suggest that destabilization is mediated by the zinc fingers of NC. Calorimetric studies reveal that NC destabilization is enthalpic in origin, probably owing to unstacking of the G-quartets upon protein binding. In contrast, parallel studies performed on a related DNA duplex reveal that under conditions where NC readily destabilizes and unfolds the quadruplexes, its effect on the DNA duplex is much less pronounced. The differences in NC's ability to destabilize quadruplex versus duplex is in accordance with the higher ΔG of melting for the latter, and with the inverse correlation between nucleic acid stability and the destabilizing activity of NC.

Original languageEnglish (US)
Pages (from-to)4395-4403
Number of pages9
JournalNucleic acids research
Issue number14
StatePublished - 2005

Bibliographical note

Funding Information:
We thank Dr Ioulia Rouzina for critical reading of the manuscript and helpful discussions, and Dr Daniel G. Mullen and Ms Brandie J. Kovaleski for chemical synthesis of NC and NC(11–55). This work was supported by NIH grant GM65056. Funding to pay the Open Access publication charges for this article was provided by NIH grant GM65056.


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