Functional role of lipids in bacterial protein translocation
|PhD ceremony:||Ms S. (Sabrina) Koch|
|When:||February 22, 2019|
|Supervisors:||prof. dr. A.J.M. (Arnold J M) Driessen, prof. dr. D.J. (Dirk-Jan) Scheffers|
|Where:||Academy building RUG|
|Faculty:||Science and Engineering|
About 30% of proteins synthesized in the cytosol of bacteria perform their function outside of the cell and either have to be inserted into or translocated across the cytoplasmic membrane. The system responsible for protein translocation is the Secretory (Sec) pathway, that in its minimal form consists of the protein-conducting membrane-embedded channel SecYEG and the motor protein SecA.
Since the Sec pathway mostly comprises of membrane proteins, studies on this system are usually done with detergent extracted proteins. However, detergents may alter structural and functional properties of proteins. We have reconstituted the protein-conducting SecYEG channel into model membranes, i.e., small nanodiscs and supported lipid bilayers, to investigate functional and mechanistic aspects of the Sec translocon in a physiologically relevant environment. This work revealed that the phospholipids of the cytoplasmic membrane do not only act as a supportive matrix for protein translocation, but that anionic phospholipids promote the functional interaction between SecYEG and SecA. Furthermore, computational studies show that anionic phospholipids localize near to the lateral gate of SecYEG, where they may facilitate the initiation of protein translocation through promoting the folding of the signal sequences of secretory proteins.