Establishing new techniques to study the cotranslational insertion and folding of membrane proteins

• Applicant: Dr. Florian Cymer
• Subject Area: Biochemistry
• Term: from 2012 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 224559867

Every cell consists of a complex membrane system that contains many different membrane proteins. Some of these proteins are main components of important metabolic pathways such as the respiratory chain and the photosystems. Other membrane proteins form channels or transmembrane receptors, which facilitate signals between cells and their environment and whose dysfunction can lead to diseases like cystic fibrosis, Alzheimer`s disease or cancer. Unfortunately very little is known about these proteins compared to water-soluble proteins, despite the fact that about one quarter of our genome encodes membrane proteins and about 50 % of all drugs target membrane proteins.Most membrane proteins are integrated into a membrane during their synthesis at a ribosome, through a membrane channel, the translocon. Since essentially nothing is known about these early integration events, I aim to study the membrane integration of pro- and eukaryotic membrane proteins.Therefore, I aim to develop molecular biology based systems that allow me and other researchers to study these early membrane integration events. The bacterial SecM protein contains an arrest peptide, which inhibits its own protein synthesis. An external pulling force on the arrested protein chain can overcome this inhibition. Therefore the arrest peptide can be used as a force sensor to study the integration of transmembrane segments. Since functionally similar arrest-sequences also exist in eukaryotes, I additionally aim to develop a system that allows me to study the insertion of eukaryotic membrane proteins into the membrane of the endoplasmic reticulum. The results will allow a better understanding of these early folding events and could explain why amino acid exchanges in transmembrane segments often lead to misfolding and disease.

• DFG Programme: Research Fellowships
• International Connection: Sweden
• Host: Professor Dr. Gunnar von Heijne
• Participating Person: Professor Dr. Dirk Schneider