Abstract
In bacteria, translocation of most soluble secreted proteins (and outer membrane proteins in Gram-negative bacteria) across the cytoplasmic membrane by the Sec machinery is mediated by the essential ATPase SecA. At its core, this machinery consists of SecA and the integral membrane proteins SecYEG, which form a protein conducting channel in the membrane. Proteins are recognised by the Sec machinery by virtue of an internally encoded targeting signal, which usually takes the form of an N-terminal signal sequence. In addition, substrate proteins must be maintained in an unfolded conformation in the cytoplasm, prior to translocation, in order to be competent for translocation through SecYEG. Recognition of substrate proteins occurs via SecA—either through direct recognition by SecA or through secondary recognition by a molecular chaperone that delivers proteins to SecA. Substrate proteins are then screened for the presence of a functional signal sequence by SecYEG. Proteins with functional signal sequences are translocated across the membrane in an ATP-dependent fashion. The current research investigating each of these steps is reviewed here.
Highlights
Sec-dependent translocation of proteins across the cytoplasmic membrane can occur by two different mechanisms: (i) a translationally coupled mechanism, which is conserved in all organisms and which is mediated by the signal recognition particle (SRP), and (ii) a bacteria-specific mechanism that is uncoupled from protein synthesis, which is mediated by the ATPase SecA (Fig. 1)
We propose a working model for targeting and translocation by the SecA-mediated translocation pathway based on the literature reviewed here: periplasmic proteins (PPs) and outer membrane proteins (OMPs) are recognised by the presence of an N-terminal signal sequence and the absence of significant tertiary structure
Substrate proteins are recognised cotranslationally by SecA, but translocation itself is uncoupled from translation and is largely post-translational, possibly resulting from the activity of Trigger Factor (TF)
Summary
Sec-dependent translocation of proteins across the cytoplasmic membrane can occur by two different mechanisms: (i) a translationally coupled mechanism, which is conserved in all organisms and which is mediated by the signal recognition particle (SRP), and (ii) a bacteria-specific mechanism that is uncoupled from protein synthesis, which is mediated by the ATPase SecA (Fig. 1). Sec substrate protein is not recognised by the SRP, it is targeted for translocation by the SecA-mediated pathway (Lee and Bernstein 2001; Schierle et al 2003). Proteins destined for SecA-mediated translocation across the membrane share two common features They contain an internally encoded targeting signal that allows them to be recognised by the Sec machinery, which usually takes the form of an N-terminal signal sequence (Hegde and Bernstein 2006). Biochemical studies have suggested that each round of ATP binding and hydrolysis results in the translocation of ∼50 amino acids (Tani et al 1989; Schiebel et al 1991; van der Wolk et al 1997), and the length of time required for translocation increases with increasing length of substrate protein (Tomkiewicz et al 2006). An uncharacterised mutation (ssaF), which is tightly linked to the yidC locus, can suppress the temperature sensitivity of a secA51 mutant (Oliver 1985)
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