TARGETING OF PROTEINS INTO PEROXISOMES

将蛋白质分类到单个亚细胞区室是至关重要的 在所有真核生物中， 细胞 因为过氧化物酶体不含DNA，所有的过氧化物酶体基质 膜蛋白必须由核基因编码，其产物是 然后再输入到细胞器中 遵循我们 发现一种作为过氧化物酶体的共有三肽 靶向信号（PTS）及其在许多过氧化物酶体中的显著保守性 蛋白质，我们计划使用生物化学，免疫学和遗传学方法 以鉴定在过氧化物酶体靶向中起作用的蛋白质。 我们 也希望了解蛋白质跨膜转运的机制， 过氧化物酶体膜。 该提案的目的是： (1)识别过氧化物酶体膜中的靶向信号 蛋白 (2)为了分析含有功能性和非功能性蛋白质的输入， 不表示 功能性PTS进入过氧化物酶体。 (3)通过以下方法鉴定、分离和表征PTS受体： 生物化学和免疫学方法。 (4)研究输入机制和方向性 的 蛋白质运输穿过过氧化物酶体膜。 (5)为了分离和表征酵母突变体， 过氧化物酶体靶向 PTS的保守性和简单性表明， 将蛋白质转运到过氧化物酶体中应该是一种很好的 蛋白质跨膜转运的一般模型。 一个 对蛋白质过氧化物酶体靶向作用的理解， 细胞中蛋白质分选的机制，并可能有助于设计 Zellweger综合征患者的合理治疗， 缺乏蛋白质进入细胞器的能力。

The sorting of proteins to individual subcellular compartments is crucial for the proper segregation of biochemical functions in all eukaryotic cells. Because peroxisomes do not contain DNA, all the peroxisomal matrix and membrane proteins must be encoded by nuclear genes whose products are then imported post-translationally into the organelle. Following our discovery of a consensus tripeptide that serves as the peroxisomal targeting signal (PTS) and its remarkable conservation in many peroxisomal proteins, we plan to use biochemical, immunological and genetic approaches to identify the proteins that play a role in peroxisomal targeting. We also wish to understand the mechanism of translocation of proteins across the peroxisomal membrane. The aims of the proposal are: (1) To identify the targeting signal in a peroxisomal membrane protein. (2) To analyze the import of proteins containing functional and non- functional PTSs into peroxisomes in vitro. (3) To identify, isolate and characterize the PTS receptor by biochemical and immunological methods. (4) To investigate the mechanism of import and the directionality of proteins transport across the peroxisomal membrane. (5) To isolate and characterize yeast mutants deficient in peroxisomal targeting. The conservation and the simplicity of the PTS suggest that the translocation of proteins into the peroxisomes should serve as an excellent model for the transport of proteins across membranes in general. An understanding of peroxisomal targeting of proteins should also shed light on the mechanisms of protein sorting in cells, and may help in the design of rational therapies for Zellweger syndrome patients who appear to be deficient in the import of proteins into the organelle.