Two modes of HIV-1 polypurine tract cleavage are affected by introducing locked nucleic acid analogs into the (-) DNA template.

The Journal of Biological Chemistry
Chandravanu DashStuart F J Le Grice

Abstract

Unusual base-pairing in a co-crystal of reverse transcriptase (RT) and a human immunodeficiency virus type 1 (HIV-1) polypurine tract (PPT)-containing RNA/DNA hybrid suggests local nucleic acid flexibility mediates selection of the plus-strand primer. Structural elements of HIV-1 RT potentially participating in recognition of this duplex include the thumb subdomain and the ribonuclease H (RNase H) primer grip, the latter comprising elements of the connection subdomain and RNase H domain. To investigate how stabilizing HIV-1 PPT structure influences its recognition, we modified the (-) DNA template by inserting overlapping locked nucleic acid (LNA) doublets and triplets. Modified RNA/DNA hybrids were evaluated for cleavage at the PPT/U3 junction. Altered specificity was observed when the homopolymeric dA.rU tract immediately 5' of the PPT was modified, whereas PPT/U3 cleavage was lost after substitutions in the adjacent dT.rA tract. In contrast, the "unzipped" portion of the PPT was moderately insensitive to LNA insertions. Although a portion of the dC.rG and neighboring dT.rA tract were minimally affected by LNA insertion, RNase H activity was highly sensitive to altering the junction between these structural elements. Using 3'...Continue Reading

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Citations

Oct 14, 2011·The Journal of Physical Chemistry. B·Smritimoy PramanikNaoki Sugimoto
Apr 11, 2008·Nucleic Acids Research·Kevin B TurnerDaniele Fabris
Jan 22, 2017·Nucleic Acids Research·Malgorzata FigielMarcin Nowotny
Jul 27, 2006·The Journal of Biological Chemistry·Chandravanu DashStuart F J Le Grice
Nov 11, 2017·The Journal of Biological Chemistry·Małgorzata FigielMarcin Nowotny
Nov 25, 2005·The Journal of Biological Chemistry·Chandravanu DashStuart F J Le Grice
Mar 22, 2005·The Journal of Biological Chemistry·Hye Young Yi-Brunozzi, Stuart F J Le Grice
Mar 28, 2009·International Journal of Molecular Sciences·Laura BonifacioMichael B Jarstfer

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