Role of lipids in membrane protein insertion (22)

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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.