NMR Structural Studies of the HIV1 RNA Packaging Element

描述（由申请人提供）：人类免疫缺陷病毒（HIV-1）通过Gag的核衣壳（NC）结构域和位于5' LTR和Gag起始位点之间的约120个核苷酸的未剪接病毒RNA区域（称为psi位点）之间的特异性相互作用来包装其基因组。HIV-1 psi位点包含4个茎环结构，命名为SL1至SL4，由相对较短的连接体连接；所有阀杆回路都需要有效封装。基因组包装是HIV-1生命周期的重要步骤；此外，越来越多的证据表明，RNA封装似乎依赖于更高阶的RNA结构。拟议研究的目标是通过核磁共振（NMR）波谱技术对psi-RNA包装元件进行结构表征，从而深入了解HIV-1基因组包装的结构决定因素。了解psi-RNA包装元件的三维结构将提供有关HIV-1基因组识别和封装的结构细节的信息，这可能反过来导致艾滋病治疗的进展。

DESCRIPTION (provided by applicant): The Human Immunodeficiency Virus (HIV-1) packages its genome by specific interactions between the nucleocapsid (NC) domain of Gag and an approximately 120 nucleotide region of the unspliced viral RNA, known as the psi-site, located between the 5' LTR and the gag initiation site. The HIV-1 psi-site contains four stem loop structures designated SL1 through SL4 connected by relatively short linkers; all stem loops are required for efficient encapsidation. Genome packaging is an essential step in the life cycle of HIV-1; furthermore, there is increasing evidence that RNA encapsidation appears to be dependent on a higher order RNA structure. The goal of the proposed research is to gain insight into the structural determinants of genome packaging in HIV-1 by structurally characterizing the psi-RNA packaging element using nuclear magnetic resonance (NMR) spectroscopy. Knowledge of the three dimensional structure of the psi-RNA packaging element will provide information I about the structural details of genome recognition and encapsidation in HIV-1, which may in turn lead to advances in AIDS therapeutics.