PROTEIN TRANSLOCATION IN YEAST

本研究的主要目的是了解 正确的蛋白质被靶向和转移的机制 在简单真核细胞中穿过内质网膜 酿酒酵母目前的模型表明，至少有 两个平行的靶向和易位途径，一个依赖于SRP， 一种是共翻译的，另一种是不依赖SRP的和翻译后的。 通过遗传和生物化学方法的结合，我们的目标是 确定催化常见反应的基因产物 两种途径或独特的一个或另一个，并了解他们的 分子功能、调节和生理重要性。 具体而言，i）我们将描述SRP和 SRP受体协调核糖体和 在一些实施方案中，核糖体可以通过转运子组分形成核糖体膜连接。 （二）我们 将表征介导不依赖SRP的 通路我们将分析这些成分如何起作用来选择蛋白质 以及它们如何将蛋白质靶向ER 膜的iii）我们将确定“适应”的分子基础， 允许细胞改善蛋白质易位的生理反应 当SRP依赖性途径被破坏时。 我们希望了解该过程的哪些方面是酵母所独有的， 这些方面可以推广到其它真核细胞和细菌。 最终，我们希望通过基因和生物化学的结合 我们将在机械的层面上理解所有人的功能， 蛋白质转运机制的细胞成分， 对于易位是必不可少的， 是调节性的。

The primary objective of the proposed research is to understand the mechanism by which the correct proteins are targeted to and translocated across the endoplasmic reticulum membrane in the simple eucaryote Saccharomyces cerevisiae. Current models suggest that there are at least two parallel targeting and translocation pathways, one SRP-dependent and co-translational, the other SRP-independent and post-translational. Through the combination of genetic and biochemical approaches, we aim to identify the gene products that catalyze the reactions that are common to both pathways or unique to one or the other and to understand their molecular function, regulation and physiological importance. Specifically, i) we will characterize the mechanism(s) by which SRP and SRP receptor coordinate the interactions between the ribosome and translocon components to form the ribosome membrane junction. ii) We will characterize the components that mediate the SRP-independent pathway. We will analyze how these components function to select proteins into this pathway, and how they function to target proteins to the ER membrane. iii) We will determine the molecular basis of "adaptation", the physiological response that allows cells to improve protein translocation when the SRP-dependent pathway is disrupted. We wish to learn which aspects of the process are unique to yeast and which aspects can be generalized to other eucaryotic cells and bacteria. Ultimately, we hope that through a combined genetic and biochemical approach, we will understand, at a mechanistic level, the function of all of the cellular constituents of the protein translocation machinery that are essential for translocation, as well as the function of those that are modulatory.