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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 人类基因组中有一个易于识别的PNPase样分子，该分子定位于线粒体及其缺乏会导致线粒体功能障碍。重要的是，我们发现体外重组SUV3和PNPase之间的直接相互作用。我们计划进一步检查它们的相互作用，以测试SUV3是否与PNPase一起监测线粒体RNA降解。降解体中还有其他蛋白质以及SUV3/PNPase吗？如果是，它们在RNA降解中的作用是什么？从线粒体中隔离和鉴定SUV3/PNPase复合物是促进当前有关哺乳动物线粒体降解体知识的关键步骤。 流感A病毒NP的晶体结构最近在Tao的实验室中确定。 NP在晶体中以三聚体的形式组织成一个两域结构，其拓扑结构与色夫病毒NP完全不同。 由残基402至428组成的短尾循环在NP寡聚化中可能起重要作用，因为该区域的单递归突变会导致寡聚的总损失。在两个域之间的界面处的NP三聚体的外部确定了一个大带电的凹槽。外部RNA结合位点表明RNA可能在流感病毒RNP中暴露于与非细分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，并阐明了RNP结构和组装，我们建议确定NP：RNA复合物的结构。