Staying straight with A-tracts: a DNA analog of the HIV-1 polypurine tract.
The polypurine tract (PPT) from the HIV-1 genome is resistant to digestion by reverse transcriptase following (-)-strand synthesis and is used to prime (+)-strand synthesis during retroviral replication. We have determined the crystal structure of the asymmetric DNA/DNA analog16-mer duplex (CTTTTTAAAAGAAAAG/CTTTTCTTTTAAAAAG) comprising most of the "visible" portion of the RNA:DNA hybrid from the polypurine tract of HIV-1, which was previously reported in a complex with HIV-1 reverse transcriptase. Our 16-mer completely encompasses a 10-mer DNA duplex analog of the HIV-1 PPT. We report here a detailed analysis of our B' form 16-mer DNA structure, including three full pure A-tracts, as well as a comparative structural analysis with polypurine tract and other A-tract-containing nucleic acid structures. Our analysis reveals that the polypurine tract structures share structural features despite being different nucleic acid forms (i.e. DNA:DNA versus RNA:DNA). In addition, the previously reported A-tract-containing DNA molecules bound to topoisomerase I are remarkably similar to our polypurine tract 16-mer structure. On the basis of our analysis, we suggest that the specific topology of long pure A-tracts is remarkably comparable across a wide array of biological environments.
Coté
Marie L
ML
Waksman Institute, Rutgers University, Piscataway, NJ 08854-8020, USA.
Pflomm
Mark
M
Georgiadis
Millie M
MM
D004264:DNA Topoisomerases, Type I / Q000737:chemistry / Q000378:metabolism; D004279:DNA, Viral / Q000737:chemistry* / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics*; D008979:Moloney murine leukemia virus / Q000201:enzymology; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization; D011061:Poly A / Q000737:chemistry* / Q000378:metabolism; D011687:Purines / Q000737:chemistry*; D012367:RNA, Viral / Q000737:chemistry; D012194:RNA-Directed DNA Polymerase / Q000737:chemistry / Q000378:metabolism
D004279:DNA, Viral; D011687:Purines; D012367:RNA, Viral; D011061:Poly A; D012194:RNA-Directed DNA Polymerase; D004264:DNA Topoisomerases, Type I