Role of lipids in membrane protein insertion (22)

该项目旨在对GET途径的受体蛋白Get1和Get2的结构和功能进行表征，Get1和Get2是完整的膜蛋白。我们发现Get1/2可以形成杂二聚体的二聚体，该二聚体含有特定的脂类。我们现在计划使用X射线结晶学和电子显微镜相结合的混合方法来确定GET受体的结构，并具体研究脂类对其结构和功能的作用。利用交联剂和具有特定修饰的脂类的MS，我们将分析它们对Get3招募和尾锚膜蛋白插入的功能影响。通过结构分析和生化分析的结合，我们将对Get1/2/3插入酶的结构和机制有一个详细的了解，并对Get途径的膜相关步骤进行剖析。

The project aims at the structural and functional characterization of the receptor proteins of the GET pathway, Get1 and Get2, which are integral membrane proteins. We showed that Get1/2 can form a dimer of the heterodimer, which contains a particular lipid species. We now plan to determine the structure of the GET receptor using a hybrid approach combining X-ray crystallography and electron microscopy, and specifically study the role of lipids on its structure and function. Using cross-linking and MS with specifically modified lipids we will analyze their functional implications for Get3 recruitment and tail-anchored membrane protein insertion. With the combination of structural and biochemical assays we will arrive at a detailed understanding of the structure and mechanism of the Get1/2/3 insertase and dissect the membrane associated steps of the GET pathway.