Targeting of proteins into peroxisomes

将蛋白质靶向过氧化物酶体

• 批准号: 8279489
• 负责人: Suresh Subramani
• 金额: $ 58.72万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-05-10 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8279489
• 关键词: Address; Affect; Back; Biochemical; Biogenesis; Biological; Biological Models; Cells; Complex; Cytosol; Disease; Docking; Eukaryotic Cell; Evolution; Genes; Growth; Health; Homeostasis; Human; Impairment; Instruction; Knowledge; Membrane Proteins; Metabolic; Morphogenesis; Nature; Organelles; Pathway interactions; Play; Positioning Attribute; Process; Protein Import; Protein translocation; Proteins; Role; Signal Transduction; Sorting - Cell Movement; Structure; Work; fascinate; lipid metabolism; peroxisome; peroxisome membrane; receptor; receptor binding; receptor recycling

The peroxisome, an essential subcellular compartment in all eukaryotic cells, is infimately involved in lipid metabolism. Work in multiple model systems has uncovered at least 32 PEX genes encoding peroxins, that play roles In peroxisome biogenesis, morphogenesis (size, volume and number), and inheritance. However, despite this wealth of knowledge regarding the proteins involved, the biochemical functions and mechanisms of acfion of most peroxins are pooriy understood. Peroxisomal proteins are targeted to the organelle matrix by two peroxisomal targefing signals, PTS1 and PTS2. PTS receptors bound to their cargo interact with the importomer, a complex of peroxisome-membrane-assoclated Pex proteins. The importomer, responsible for peroxisomal matrix protein translocation is comprised ofthe docking and RING subcomplexes. During the matrix protein import cycle, the receptor-cargo complexes shuttle from the cytosol, interact with the importomer, release cargo in the peroxisome matrix and the receptors then shutfie back to the cytosol, aided by a receptor-recycling subcomplex. Major unanswered questions in the peroxisome biogenesis field relate to the exact nature, function and structure ofthe unusual peroxisomal translocon which, unlike translocons associated with other subcellular compartments, transports folded and oligomeric proteins across (Aimi). The evolution of dual matrix protein import pathways and the steps in cargo release and receptor recycling from peroxisomes. Involving the function of Pex8, are critical for an understanding of the import cycle (Aim 2). The recent emergence of a clear involvement of the endoplasmic reficulum (ER) in peroxisome morphogenesis, and even biogenesis, raises important quesfions about the machinery that sorts peroxisomal membrane proteins via the ER and the funcfional role of this pathway in peroxisome growth and division (Aim 3). Finally, we wish to further explore fascinating emerging clues regarding a crosstalk between peroxisome biogenesis, inheritance and turnover (Aim 4). We believe we are uniquely positioned to answer these fundamentally important cell biological quesfions that seriously impact human health and disease.

过氧酶体是所有真核细胞中必不可少的一个亚细胞室，与脂类密切相关。 新陈代谢。在多个模型系统中的工作已经发现了至少32个编码过氧化物素的PEX基因， 在过氧化体的生物发生、形态发生(大小、体积和数量)和遗传中发挥作用。然而， 尽管关于所涉及的蛋白质有如此丰富的知识，但生物化学功能和 大多数过氧化物酶的作用机制尚不清楚。过氧化体蛋白的靶标是 细胞器基质通过两个过氧化体靶标信号，pts1和pts2。PTS受体与其货物结合 与进口体相互作用，这是一种过氧酶体-膜-关联的Pex蛋白的复合体。这个 负责过氧化体基质蛋白转位的重要分子由对接和环组成 亚复合体。在基质蛋白输入周期中，受体-货物复合体从 胞浆，与重要分子相互作用，释放过氧化体基质和受体中的货物，然后关闭 在受体回收亚复合体的帮助下，回到细胞质中。中未回答的主要问题 过氧酶体生物发生领域涉及到异常过氧酶体的确切性质、功能和结构 与与其他亚细胞隔室相关的转运子不同，转运子是折叠的和 寡聚蛋白(AIMI)。双重基质蛋白输入途径的进化及其在体内的研究进展 过氧化体的货物释放和受体回收。涉及Pex8的功能，对于 了解进口周期(目标2)。最近出现的一种明显的内质参与 在过氧化体形态发生，甚至生物发生中的反射(ER)，提出了关于 通过内质网对过氧化体膜蛋白进行分类的机制以及这一途径在体内的功能作用 过氧化物体的生长和分裂(目标3)。最后，我们希望进一步探索引人入胜的新线索 关于过氧化物体生物发生、遗传和更替之间的串扰(目标4)。我们相信我们是 独特的定位来回答这些根本上重要的细胞生物学问题 人类的健康和疾病。