PROTEIN TRANSPORT INTO MAMMALIAN ENDOPLASMIC RETICULUM

该项目的长期目标是了解蛋白质跨膜转运或插入哺乳动物内质网（ER）膜的分子机制。 我们已经建立了具有纯化膜蛋白组分的重组蛋白脂质体和可溶性系统，可以重现整个转运过程和部分反应。 ER膜的最小易位装置仅包含异源三聚体Sec61p复合物、TRAM蛋白和SRP受体。 我们现在建议对易位的机制进行彻底的分析。 具体来说，我们将使用问题：1。共翻译易位是如何启动的？2.核糖体如何与Sec61 p通道相互作用？3.膜蛋白是如何插入脂质双层的？4. Sec62p和Sec63p的哺乳动物同源物的功能是什么？这些研究将大大有助于我们理解的第一个和决定性的步骤，在生物合成的一个大类蛋白质，蛋白质的质膜，溶酶体，和所有细胞器的分泌途径。

The long-term goal of this project is to understand the molecular mechanism by which proteins are transported across or are inserted into the mammalian endoplasmic reticulum (ER) membrane. We have established reconstituted proteoliposome and soluble systems with purified membrane protein components which reproduce the overall translocation process and partial reactions. The minimum translocation apparatus of the ER membrane comprises only the heterotrimeric Sec61p complex, the TRAM protein, and the SRP receptor. We now propose to perform a thorough analysis of the mechanism of translocation. Specifically, we will use questions: 1. How is cotranslational translocation initiated? 2. How do ribosomes interact with the Sec61p channel? 3. How are membrane proteins inserted into the lipid bilayer? 4. What is the function of the mammalian homologs of Sec62p and Sec63p? These studies will contribute significantly to our understanding of the first and decisive step in the biosynthesis of a large of class proteins, proteins of the plasma membrane, of lysosomes, and of all organelles of the secretory pathway.