Characterization of the interaction of Get3 with the membrane bound receptors Get1 and Get2

• Applicant: Professor Dr. Volker Dötsch
• Subject Area: Biochemistry
• Term: from 2012 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 217561225

The insertion of membrane proteins into the correct membrane of a cell is an important cellular task. A special class of membrane proteins, called tail-anchored proteins, consist of an N-terminal soluble domain and a single C-terminal transmembrane helix. Insertion of these tail-anchored proteins into membranes requires a specialized machinery that includes several soluble and membrane-bound components. After synthesis at the ribosome the transmembrane helix of the tail-anchored protein is loaded into a hydrophobic groove on the protein Get3. This protein interacts in an ATP-dependent manner with the two membrane bound receptors Get1 and Get2. While Get2 is important for recruiting Get3 to the membrane, the interaction with Get1 opens the closed conformation of Get3 and initiates the insertion process. Recently we have solved the structures of Get3 in complex with the soluble domains of Get1 and Get2. Based on these results we now propose to investigate the structure and function of the entire complex including the transmembrane parts. Both receptors consist of three transmembrane helices each and were shown to form a tight complex. We will use mutagenesis analysis and insertion assays to further characterize this crucial process.

• DFG Programme: Research Grants
• International Connection: USA
• Participating Persons: Dr. Frank Bernhard; Professor Dr. Vlad Denic