Substrate-induced assembly and functional mechanism of the membrane protein insertase SecYEG-YidC.

Substrate-induced assembly of SecYEG-YidC facilitates membrane protein insertion without gate entry, revealing a conserved, thermodynamically driven mechanism.

• Why it matters: Understanding how membrane proteins are assembled is crucial for insights into cell function and disease, yet the molecular cooperation between translocons and insertases remains unclear.
• What they did: Using cryo-EM and cell-free synthesis, the study visualized NuoK biogenesis, showing its nascent chain bypasses the SecYEG lateral gate and recruits YidC at the translocon’s back side in a substrate-dependent manner.
• The result: Findings highlight YidC’s extensive contact with the nascent chain and its role in early folding, supporting a conserved, gate-independent insertion pathway that advances models of membrane protein biogenesis.