SecYEGSecA

SecYEGSecA refers to the functional complex formed by the bacterial SecYEG translocon together with the cytosolic ATPase SecA, which together mediate Sec-dependent protein translocation across the inner membrane. The SecYEG core is a membrane-embedded channel composed of SecY, SecE, and SecG. SecA associates with the cytosolic face of SecYEG and uses energy from ATP hydrolysis to drive polypeptide movement through the channel. Substrates are typically preproteins bearing N-terminal signal peptides and, in many bacteria, are maintained in a translocation-competent state by chaperones such as SecB before engagement with SecA.

Structure and substrate engagement: SecY forms the central pore, with SecE and SecG supporting channel stability and modulating gating. A plug domain helps seal the channel in the resting state, while a lateral gate allows membrane proteins destined for the lipid phase to integrate laterally into the bilayer. When a substrate is engaged, SecA binds the signal peptide and the polypeptide, coupling its ATP-driven conformational changes to translocation through SecYEG.

Mechanism: The SecA motor interacts with SecYEG on the cytosolic side and cycles between different nucleotide states to push segments of the polypeptide through the channel in steps. Translocation often proceeds with SecB or other chaperones aiding substrate delivery and prevention of premature folding. In addition to transporting secreted proteins, SecYEG also contributes to the insertion of some membrane proteins via the lateral gate.

Variation and significance: Some bacteria possess SecA2 systems for specialized substrates. The SecYEG–SecA mechanism is essential for viability in most bacteria and is a target for antibiotics; structurally, it is related to the eukaryotic Sec61 translocon, reflecting a conserved protein translocation strategy across domains of life.