TARGETING OF PROTEINS INTO PEROXISOMES

将蛋白质分选到各个亚细胞室是至关重要的。 在所有真核生物中适当地分离生化功能 细胞。因为过氧化体不含DNA，所以所有的过氧化体基质 膜蛋白必须由核基因编码，其产物是 然后以翻译后的方式输入细胞器。遵循我们的 一种具有过氧化体功能的共识三肽的发现 靶向信号(PTS)及其在多种过氧化体中的显著保守性 蛋白质，我们计划使用生化、免疫学和遗传学方法 以确定在过氧化体靶向中起作用的蛋白质。我们 我也想了解蛋白质跨膜转运的机制 过氧化物酶体膜。这项建议的目的是： (1)识别过氧化体膜中的靶向信号 蛋白。 (2)分析含有功能性和非功能性的蛋白质的进口 在体外将功能性PTS转化为过氧体。 (3)鉴定、分离和鉴定PTS受体 生化和免疫学方法。 (4)调查进口机制和进口的方向性 蛋白质通过过氧体的膜运输。 (5)分离和鉴定缺陷酵母突变株 过氧化物体靶向。 PTS的保守性和简单性表明， 蛋白质转位到过氧化体中应该是一种极好的 一般情况下蛋白质跨膜运输的模型。一个 理解蛋白质的过氧化体靶向也应该会有所帮助。 关于细胞中蛋白质分选的机制，并可能有助于设计 对Zellweger综合征患者的合理治疗 缺乏将蛋白质输入细胞器的。

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.