Signal peptides are allosteric activators of the protein translocase

Most secreted proteins contain a cleavable N-terminal signal sequence that mediates their targeting and translocation across membranes. In bacteria, the protein translocation channel is comprised of the SecYEG channel and the ATPase motor, SecA. Targetting of proteins to SecA is thought to involve signal sequence recognition. Gouridis et al. demonstrate that signal sequences have a novel role beyond protein targeting. They can act in trans and allosterically activate the SecYEG translocase. Translocase activation proceeds through two consecutive but distinct signal-peptide-driven states. This study sheds light on a fundamental cellular process.