NMR 检测 HIV-1 5'-leader RNA 中调节基因组包装的结构。
NMR detection of structures in the HIV-1 5'-leader RNA that regulate genome packaging.
机构信息
Howard Hughes Medical Institute (HHMI) and Department of Chemistry and Biochemistry, University of Maryland Baltimore County (UMBC), Baltimore, MD 21250, USA.
出版信息
Science. 2011 Oct 14;334(6053):242-5. doi: 10.1126/science.1210460.
Abstract
The 5'-leader of the HIV-1 genome regulates multiple functions during viral replication via mechanisms that have yet to be established. We developed a nuclear magnetic resonance approach that enabled direct detection of structural elements within the intact leader (712-nucleotide dimer) that are critical for genome packaging. Residues spanning the gag start codon (AUG) form a hairpin in the monomeric leader and base pair with residues of the unique-5' region (U5) in the dimer. U5:AUG formation promotes dimerization by displacing and exposing a dimer-promoting hairpin and enhances binding by the nucleocapsid (NC) protein, which is the cognate domain of the viral Gag polyprotein that directs packaging. Our findings support a packaging mechanism in which translation, dimerization, NC binding, and packaging are regulated by a common RNA structural switch.
摘要
HIV-1 基因组的 5'-leader 通过尚未确定的机制调节病毒复制过程中的多种功能。我们开发了一种核磁共振方法，能够直接检测完整的 leader（712 个核苷酸二聚体）中的结构元件，这些结构元件对于基因组包装至关重要。跨越 gag 起始密码子（AUG）的残基在单体 leader 中形成发夹结构，并与二聚体中的独特 5' 区域（U5）的残基形成碱基对。U5:AUG 的形成通过置换和暴露二聚体促进发夹结构，并增强核衣壳（NC）蛋白的结合，NC 蛋白是指导包装的病毒 Gag 多蛋白的同源结构域。我们的发现支持一种包装机制，其中翻译、二聚化、NC 结合和包装受一个共同的 RNA 结构开关调节。
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