Mechanism of the translocon: events at the gate

Bacteria confine their bodily features by membranes that separate the interior from the external environment. Bacteria have developed various systems to communicate across this barrier membrane and conduct essential cellular processes such as growth and development. The main barrier that can be found throughout different forms of life is the inner or cytoplasmic membrane. This layer is composed of a bilayer of phospholipids and contains various cellular machineries that help to maintain a metabolic balance, preventing unintended loss of cellular components as well as the uptake of essential nutrients. The membrane is impermeable to small solutes, proteins and other cellular components, therefore, proteins needs to be actively transported to the exterior. To do so, selective translocation machineries in the membrane allow proteins to pass the membrane in a carefully orchestrated manner. This process of protein secretion has been extensively studied in the model bacteria Escherichia coli. The major and universally conserved route for protein transport into and across membrane is the Sec pathway. Proteins destined to be localized outside the cytoplasmic membrane are recognized via their signal sequence by the SecA motor protein, which in turn associates with the membrane-residing SecYEG channel and followed by a traverse of the unfolded protein through SecYEG channel. The work in this thesis extents the current knowledge and has provided insight in how subunits of the translocon work cooperatively to guide polypeptides across the membrane. However, still many questions remain. The exact mechanism by which SecA drives proteins through the channel remains to be elucidate.