Introduction

Protein concentration in the cell is a function of the rates of protein synthesis and destruction, and the regulation of both processes is necessary for a properly functioning cell. The degradation of proteins is mainly performed by a small number of ATP-dependent cellular proteases. ATP-dependent proteases are molecular motors that degrade substrates by translocating along the substrates’ polypeptide chain. Degradation is directional, highly processive, and requires energy from ATP hydrolysis (Kim et al., 2000; Lee et al., 2001; Reid et al., 2001; Kenniston et al., 2003; Aubin-Tam et al., 2011; Maillard et al., 2011). In this manner, these proteases control the concentrations of hundreds of regulatory proteins involved in processes such as the cell cycle, transcription, and signal transduction and play an important housekeeping role by destroying misfolded and damaged proteins (Ciechanover, 1994; Glickman and Ciechanover, 2002; Goldberg, 2003; Collins and Tansey, 2006). Despite this wide range of substrates, proteases have to act specifically to avoid the unintended degradation of the rest of the cellular proteins. ATP-dependent proteases in Bacteria, Archaea, and Eukaryotes have evolved a similar way of solving this problem: their proteolytic sites are encapsulated within the protease structure where they are inaccessible to folded proteins (Baumeister et al., 1998). Substrates are targeted to the proteases via specific degradation signals, to be unraveled and translocated into the proteolytic chamber (Baker and Sauer, 2006; Schrader et al., 2009). The unfolding and translocation of substrates is accelerated by ATP hydrolysis and is catalyzed by ATPase domains or subunits that flank the proteolytic barrel and pull at the substrates’ polypeptide chains (Prakash and Matouschek, 2004, Sauer et al., 2004; Aubin-Tam et al., 2011; Maillard et al., 2011). In this chapter, we will introduce the main ATP-dependent proteases in Bacteria, Archaea, and Eukaryotes and attempt to describe the common mechanisms through which they recognize and degrade their substrates.