NMR Structural Studies of the HIV1 RNA Packaging Element

描述(申请人提供)：人类免疫缺陷病毒(HIV-1)通过Gag的核衣壳(NC)结构域与非剪接病毒RNA的约120个核苷酸区域之间的特定相互作用来包装其基因组，该区域称为psi位点，位于5‘LTR和Gag起始点之间。HIV-1 psi位点包含四个茎环结构，命名为SL1到SL4，由相对较短的连接子连接；所有的茎环都是有效包裹所必需的。基因组包装是HIV-1生命周期中必不可少的一步；此外，越来越多的证据表明，RNA的封装似乎依赖于更高阶的RNA结构。这项拟议的研究的目标是通过使用核磁共振(NMR)光谱对psi-RNA包装元件进行结构表征，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基因组识别和包裹的结构细节的信息，这可能反过来导致艾滋病治疗的进步。

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.