Poster abstracts

Poster number 31 submitted by Gabrielle Todd

NMR Characterization of Neomycin Binding to HIV-1 SL-1 RNA

Gabrielle Todd (Chemical Biology, University of Michigan), Xiaoyan Sun (Chemistry, University of Michigan), Max Bailor, Qi Zhang (Chemistry, University of Michigan), Hashim Al-Hashimi (Biophysics, University of Michigan)

Abstract:
As in all reteroviruses, two identical copies of genomic RNA are packaged in the viral particles of the Human Immunodeficiency Virus Type I (HIV-1). The two RNA strands are held together in a non-covalent dimer the integrity of which is important in multiple steps of the viral life-cycle, including reverse transcription, recombination, RNA packaging, and viral infectivity. For this reason, SL-1 is a possible RNA target for developing anti-HIV therapeutics. In addition to a self-complementary palindromic loop, SL-1 contains a highly conserved G-rich bulge which has been shown to be critical for genome dimerization and packaging. Here, we show using NMR that the aminoglycoisde neomycin B binds specifically to the SL-1 bulge. The site of recognition maps to specific regions of high electronegative charge density where Mg2+ binding is also observed. We present initial data aimed at characterizing how neomycin B recognition affects the global and local structural dynamics of SL-1 and how this in turn compares with Mg2+ binding. When combined with previous studies showing neomycin B binding to the SL-1 loop, our data suggests that up to four unique binding sites in SL-1 dimers are available for targeting using therapeutic compounds.

Keywords: HIV-1 SL-1 RNA, NMR