NMR Structural Studies of the HIV1 RNA Packaging Element

描述（由申请方提供）：人类免疫缺陷病毒（HIV-1）通过Gag的核衣壳（NC）结构域与未剪接病毒RNA的约120个核苷酸区域（称为psi位点，位于5' LTR和gag起始位点之间）之间的特异性相互作用包装其基因组。 HIV-1 psi位点包含四个茎环结构，命名为SL 1至SL 4，由相对较短的接头连接;所有茎环都是有效的双糖苷化所必需的。 基因组包装是HIV-1生命周期中的一个重要步骤;此外，越来越多的证据表明，RNA包装似乎依赖于更高级的RNA结构。 拟议研究的目标是通过使用核磁共振（NMR）光谱在结构上表征psi-RNA包装元件，深入了解HIV-1基因组包装的结构决定因素。 对psi-RNA包装元件的三维结构的了解将提供关于HIV-1中基因组识别和折叠的结构细节的信息，这反过来可能导致AIDS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.