Dynamics and flexibility of the SecYEG translocation channel

Every form of life requires the presence of a lipid membrane to separate the interior aqueous compartment from the external environment and to ensure proper functioning of the cell. The lipid bilayer functions as a hydrophobic matrix embedding integral membrane proteins, but it acts also as an active barrier that controls the permeation of small and large molecules entering or leaving the cell. Transport across the lipid membrane is mediated by integral membrane proteins, which allow for the selective permeability of the membrane. In Escherichia coli, about 30% of the proteins synthesized in the cell accomplish their function outside the cytoplasm. For this reason, every cell contains dedicated transport systems that translocate or insert proteins across or into the cytoplasmic membrane. In bacteria, the main system is termed the Sec translocase, with as its central component a membrane-embedded protein-conducting channel, the SecYEG complex (also termed translocon). This thesis focuses on the bacterial translocon and employs organic synthetic chemistry to provide new functionalities to the translocation channel and to substrate proteins in order to obtain a detailed understanding of the functional aspects of the SecYEG channel.