Skip Navigation


Nucleic Acids Research Advance Access first published online on April 9, 2008
This version published online on April 17, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn129
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (2757K) Freely available
Right arrow Screen PDF (596K) Freely available
Right arrowOA All Versions of this Article:
36/8/2799    most recent
gkn129v2
gkn129v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Turner, K. B.
Right arrow Articles by Fabris, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Turner, K. B.
Right arrow Articles by Fabris, D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Structural Biology

Structural probing of the HIV-1 polypurine tract RNA:DNA hybrid using classic nucleic acid ligands

Kevin B. Turner1, Robert G. Brinson2,3, Hye Young Yi-Brunozzi3, Jason W. Rausch3, Jennifer T. Miller3, Stuart F.J. Le Grice3, John P. Marino2 and Daniele Fabris1,*

1University of Maryland Baltimore County, Baltimore, 2Center for Advanced Research in Biotechnology of the University of Maryland Biotechnology Institute and the National Institute of Standards and Technology, Rockville, and 3HIV Drug Resistance Program, NCI, National Institutes of Health, Frederick, MD, USA

*To whom correspondence should be addressed. Tel: +1 410 455 3053; Fax: +1 410 455 2608; Email: fabris{at}umbc.edu Correspondence may also be addressed to John P. Marino. Tel: +1 240 314 6160; Fax: +1 240 314 6255; Email: marino{at}umbi.umd.edu

Received January 5, 2008. Revised February 22, 2008. Accepted March 9, 2008.

The interactions of archetypical nucleic acid ligands with the HIV-1 polypurine tract (PPT) RNA:DNA hybrid, as well as analogous DNA:DNA, RNA:RNA and swapped hybrid substrates, were used to probe structural features of the PPT that contribute to its specific recognition and processing by reverse transcriptase (RT). Results from intercalative and groove-binding ligands indicate that the wild-type PPT hybrid does not contain any strikingly unique groove geometries and/or stacking arrangements that might contribute to the specificity of its interaction with RT. In contrast, neomycin bound preferentially and selectively to the PPT near the 5'(rA)4:(dT)4 tract and the 3' PPT-U3 junction. Nuclear magnetic resonance data from a complex between HIV-1 RT and the PPT indicate RT contacts within the same regions highlighted on the PPT by neomycin. These observations, together with the fact that the sites are correctly spaced to allow interaction with residues in the ribonuclease H (RNase H) active site and thumb subdomain of the p66 RT subunit, suggest that despite the long cleft employed by RT to make contact with nucleic acids substrates, these sites provide discrete binding units working in concert to determine not only specific PPT recognition, but also its orientation on the hybrid structure.

The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 RNAHome page
K. B. Turner, H. Y. Yi-Brunozzi, R. G. Brinson, J. P. Marino, D. Fabris, and S. F.J. Le Grice
SHAMS: Combining chemical modification of RNA with mass spectrometry to examine polypurine tract-containing RNA/DNA hybrids
RNA, August 1, 2009; 15(8): 1605 - 1613.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
K. Post, B. Kankia, S. Gopalakrishnan, V. Yang, E. Cramer, P. Saladores, R. J. Gorelick, J. Guo, K. Musier-Forsyth, and J. G. Levin
Fidelity of plus-strand priming requires the nucleic acid chaperone activity of HIV-1 nucleocapsid protein
Nucleic Acids Res., April 1, 2009; 37(6): 1755 - 1766.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.