This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Prof. Charles P. Scholes from Albany University is actively studying the mechanisms underlying HIV-1 replication. A critical step in HIV-1 replication is reverse transcription of HIV-1 genomic RNA to double-stranded DNA by reverse transcriptase (RT). Two viral proteins, the RT enzyme and a small nucleocapsid protein NCp7, which is well-known nucleic acid chaperone direct this process. At the beginning of the linear DNA synthesis, the newly made minus-strand strong-stop DNA ((-)ssDNA) is transferred to the 3'end of the genomic RNA by means of an hybridization reaction between transactivation response element (TAR) RNA and cTAR DNA sequences. Since both TAR sequences exhibit stable hairpin structures, NCp7 needs to destabilize the TAR structures in order to chaperone their hybridization. NCp7 is characterized by two zinc fingers that plays a key role in HIV-1 life cycle and presents a promising target for an antiviral therapy. It has been shown that NCp7 chaperones the first strand transfer by promoting the annealing of the complementary transactivation response element (TAR) RNA and cTAR DNA stem-loop sequences. This critically relies on NCp7 ability to transiently melt their terminal base pairs. The destabilization activity of NCp7 is mediated by a hydrophobic plateau at the surface of the folded zinc fingers, which restricted the oligonucleotide flexibility. The destabilizing of the TAR and cTAR sequences can be mediated by a single finger motif, while the annealing activity requires the two fingers. NCp7 induces a limited destabilization of the primer binding site (PBS) stem-loops involved in the second strand transfer. However, NCp7 can chaperone their homodimerization, by stabilizing the annealing of their partly self-complementary loops. The propensity of NCp7 to promote the dimerization of partly complementary sequences may favor secondary contacts between viral sequences and thus, recombination and viral diversity. Moreover, NCp7 promotes the second strand transfer, by chaperoning a kissing-loop intermediate, through an extension of the loops and a weakening of the upper base pair of the stem.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Biotechnology Resource Grants (P41)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-BCMB-K (40))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Cornell University
Schools of Arts and Sciences
United States
Zip Code
Jain, Rinku; Vanamee, Eva S; Dzikovski, Boris G et al. (2014) An iron-sulfur cluster in the polymerase domain of yeast DNA polymerase ?. J Mol Biol 426:301-8
Pratt, Ashley J; Shin, David S; Merz, Gregory E et al. (2014) Aggregation propensities of superoxide dismutase G93 hotspot mutants mirror ALS clinical phenotypes. Proc Natl Acad Sci U S A 111:E4568-76
Georgieva, Elka R; Borbat, Peter P; Ginter, Christopher et al. (2013) Conformational ensemble of the sodium-coupled aspartate transporter. Nat Struct Mol Biol 20:215-21
Airola, Michael V; Sukomon, Nattakan; Samanta, Dipanjan et al. (2013) HAMP domain conformers that propagate opposite signals in bacterial chemoreceptors. PLoS Biol 11:e1001479
Airola, Michael V; Huh, Doowon; Sukomon, Nattakan et al. (2013) Architecture of the soluble receptor Aer2 indicates an in-line mechanism for PAS and HAMP domain signaling. J Mol Biol 425:886-901
Sun, Yan; Zhang, Ziwei; Grigoryants, Vladimir M et al. (2012) The internal dynamics of mini c TAR DNA probed by electron paramagnetic resonance of nitroxide spin-labels at the lower stem, the loop, and the bulge. Biochemistry 51:8530-41
Smith, Andrew K; Freed, Jack H (2012) Dynamics and ordering of lipid spin-labels along the coexistence curve of two membrane phases: an ESR study. Chem Phys Lipids 165:348-61
Yu, Renyuan Pony; Darmon, Jonathan M; Hoyt, Jordan M et al. (2012) High-Activity Iron Catalysts for the Hydrogenation of Hindered, Unfunctionalized Alkenes. ACS Catal 2:1760-1764
Gaffney, Betty J; Bradshaw, Miles D; Frausto, Stephen D et al. (2012) Locating a lipid at the portal to the lipoxygenase active site. Biophys J 103:2134-44
Dzikovski, Boris; Tipikin, Dmitriy; Freed, Jack (2012) Conformational distributions and hydrogen bonding in gel and frozen lipid bilayers: a high frequency spin-label ESR study. J Phys Chem B 116:6694-706

Showing the most recent 10 out of 72 publications