Signal peptides are allosteric activators of the protein translocase.
Extra-cytoplasmic polypeptides are usually synthesized as 'preproteins' carrying amino-terminal, cleavable signal peptides and secreted across membranes by translocases. The main bacterial translocase comprises the SecYEG protein-conducting channel and the peripheral ATPase motor SecA. Most proteins destined for the periplasm and beyond are exported post-translationally by SecA. Preprotein targeting to SecA is thought to involve signal peptides and chaperones like SecB. Here we show that signal peptides have a new role beyond targeting: they are essential allosteric activators of the translocase. On docking on their binding groove on SecA, signal peptides act in trans to drive three successive states: first, 'triggering' that drives the translocase to a lower activation energy state; second, 'trapping' that engages non-native preprotein mature domains docked with high affinity on the secretion apparatus; and third, 'secretion' during which trapped mature domains undergo several turnovers of translocation in segments. A significant contribution by mature domains renders signal peptides less critical in bacterial secretory protein targeting than currently assumed. Rather, it is their function as allosteric activators of the translocase that renders signal peptides essential for protein secretion. A role for signal peptides and targeting sequences as allosteric activators may be universal in protein translocases.
Gouridis
Giorgos
G
Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology-Hellas, Iraklio, Crete 71110, Greece.
Karamanou
Spyridoula
S
Gelis
Ioannis
I
Kalodimos
Charalampos G
CG
Economou
Anastassios
A
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D020536:Enzyme Activators / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D033903:Periplasmic Proteins / Q000378:metabolism; D011485:Protein Binding; D021382:Protein Sorting Signals / Q000502:physiology*; D021381:Protein Transport
D020536:Enzyme Activators; D029968:Escherichia coli Proteins; D033903:Periplasmic Proteins; D021382:Protein Sorting Signals; D000469:Alkaline Phosphatase; D000251:Adenosine Triphosphatases