PNPASE COMPLEX

PNP酶复合物

• 批准号: 7953810
• 负责人: Wen-Hwa Lee
• 金额: $ 0.87万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7953810
• 关键词: Binding Sites; Charge; Complex; Computer Retrieval of Information on Scientific Projects Database; Electron Microscopy; Funding; Grant; Human Genome; In Vitro; Influenza A virus; Institution; Knowledge; Laboratories; Mitochondria; Mitochondrial RNA; Modeling; Monitor; Mutation; Play; Proteins; RNA; RNA Binding; RNA Degradation; RNA Viruses; Recombinants; Research; Research Personnel; Resources; Rhabdoviridae; Role; Source; Structure; Tail; Testing; United States National Institutes of Health; Work; degradosome; influenzavirus; macromolecule; mitochondrial dysfunction

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There is a readily recognizable PNPase-like molecule in human genome, which localizes to mitochondria and its deficiency leads to mitochondrial dysfunction. Importantly, we have found that a direct interaction between recombinant SUV3 and PNPase in vitro. We plan to further examine their interaction in detail to test whether SUV3 works in concert with PNPase in monitoring mitochondrial RNA degradation. Are there other proteins in degradosome together with SUV3/PNPase? If yes, what are their roles in RNA degradation? To isolate and identify the SUV3/PNPase complex from mitochondria are critical steps in advancing the current knowledge on mammalian mitochondrial degradosome. The crystal structure of influenza A virus NP has recently been determined in Tao's laboratory. Organized as trimers in the crystal, NP folds into a two-domain structure with a topology completely different from that of the rhabdovirus NP. A short tail loop, consisting of residues 402 to 428, is likely to play an important role in NP oligomerization, as single-residue mutation in this region causes a total loss of oligomerization. A large positively charged groove was identified at the exterior of the NP trimer at the interface between the two domains. An external RNA binding site indicates that RNA is likely to be exposed in the influenza virus RNPs, different from the situation in non-segmented RNA viruses [2]. To provide a definite evidence for our external RNA binding model and to elucidate RNP structure and assembly, we propose to determine the structure of the NP:RNA complex.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 人类基因组中有一种易于识别的 PNPase 样分子，其定位于线粒体，其缺陷会导致线粒体功能障碍。重要的是，我们在体外发现重组 SUV3 和 PNPase 之间存在直接相互作用。我们计划进一步详细研究它们的相互作用，以测试 SUV3 是否与 PNPase 协同监测线粒体 RNA 降解。降解体中是否还有其他蛋白质与 SUV3/PNPase 一起？如果是，它们在 RNA 降解中起什么作用？从线粒体中分离和鉴定 SUV3/PNPase 复合物是推进当前哺乳动物线粒体降解体知识的关键步骤。 陶教授的实验室最近确定了甲型流感病毒NP的晶体结构。 NP 在晶体中以三聚体形式组织，折叠成双结构域结构，其拓扑结构与弹状病毒 NP 完全不同。 由残基 402 至 428 组成的短尾环可能在 NP 寡聚化中发挥重要作用，因为该区域的单残基突变会导致寡聚化完全丧失。在两个结构域之间的界面处的 NP 三聚体外部发现了一个大的带正电荷的凹槽。外部RNA结合位点表明流感病毒RNP中RNA很可能暴露，这与非节段RNA病毒的情况不同[2]。为了为我们的外部RNA结合模型提供明确的证据并阐明RNP结构和组装，我们建议确定NP:RNA复合物的结构。