Sec translocon has an insertase-like function in addition to polypeptide conduction through the channel.

Area of Science:

• Molecular Biology
• Membrane Protein Biogenesis
• Cellular Transport

Background:

• The Sec translocon is a protein channel crucial for translocating polypeptides across membranes.
• Its lateral gate facilitates the exit of hydrophobic segments for membrane integration.
• Existing models partially explain translocon function, particularly regarding hydrophilic polypeptide translocation.

Purpose of the Study:

• To elucidate the mechanism of *de novo* membrane protein insertion by the Sec translocon.
• To investigate the role of the lateral gate in *de novo* insertion.
• To compare *de novo* insertion with insertase mechanisms.

Main Methods:

• Analysis of recent structural studies on translocon function.
• Comparative analysis of protein insertion mechanisms.

Main Results:

• The Sec translocon has a dual function: polypeptide translocation and *de novo* membrane insertion.
• *De novo* insertion of N-terminal topogenic segments utilizes the lateral gate, not the polypeptide-conducting channel.
• The *de novo* insertion mechanism resembles that of insertases like YidC and EMC3.

Conclusions:

• The Sec translocon's *de novo* insertion function is distinct from its translocation channel.
• The lateral gate is a key site for initiating *de novo* membrane protein insertion.
• This insertion process involves an intramembrane surface, acting as a halfway point for integration.