The Sec machinery is essential for life. All cells need to assemble phospholipid bilayer membranes, which have embedded proteins. In bacteria, the Sec pathway catalyses most of the load of protein secretion and acts as the front end for several subsequent protein-sorting and sub-cellular-targeting machines.
A combination of membrane-embedded and soluble factors that contribute to pre-protein targeting and translocation are described. A membrane-embedded pre-protein-conducting channel and an ATPase motor lie at its core.
Atomic resolution structures of the pre-protein-conducting channel, its ATPase motor and targeting chaperones are available.
The protein-conducting channel is composed of several tilted and straight helices of varying lengths and is gated by a periplasmic plug. It has a well-characterized closed state and an anticipated open state that is expected to result from dilation.
Metabolic energy in the form of both ATP and the proton motive force is used to power pre-protein movement through the translocase machine.
The available data allow for a synthesis of multiple sub-reactions into a coherent model. This model describes how the translocase recognizes secretory proteins at specific sites and how it subsequently promotes protein export by a series of distinct energy-driven conformational states.
All cells must traffic proteins across their membranes. This essential process is responsible for the biogenesis of membranes and cell walls, motility and nutrient scavenging and uptake, and is also involved in pathogenesis and symbiosis. The translocase is an impressively dynamic nanomachine that is the central component which catalyses transmembrane crossing. This complex, multi-stage reaction involves a cascade of inter- and intramolecular interactions that select, sort and target polypeptides to the membrane, and use energy to promote the movement of these polypeptides across — or their lateral escape and integration into — the phospholipid bilayer, with high fidelity and efficiency. Here, we review the most recent data on the structure and function of the translocase nanomachine.
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We are grateful to the Kalodimos laboratory for an exciting collaboration and to B. Kalodimos and T. Pugsley for stimulating discussions. Research in our laboratory is supported by grants from the European Union (LSHG-CT-2005-037586), the Greek General Secretariat of Research and the European Regional Development Fund (01AKMON46 and PENED03ED623).
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Papanikou, E., Karamanou, S. & Economou, A. Bacterial protein secretion through the translocase nanomachine. Nat Rev Microbiol 5, 839–851 (2007). https://doi.org/10.1038/nrmicro1771
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