THERMODYNAMICS OF THE PROTEIN TRANSLOCATION

Many proteins synthesized in bacteria are secreted from the cytoplasm into the periplasm to function in the cell envelope or in the extracellular medium. The Sec translocase is a primary and evolutionary conserved secretion pathway in bacteria. It catalyzes the translocation of unfolded proteins across the cytoplasmic membrane via the pore-forming SecYEG complex. This process is driven by the proton motive force and ATP hydrolysis facilitated by the SecA motor protein. Current insights in the mechanism of protein translocation are largely based on elaborate multidisciplinary studies performed during the last three decades. To understand the process dynamics, the thermodynamic principles of translocation and the subunit interactions need to be addressed. Isothermal titration calorimetry has been widely applied to study thermodynamics of biological interactions, their stability, and driving forces. Here, we describe the examples that exploit this method to investigate key interactions among components of the Sec translocase and suggest further potential applications of calorimetry.