insertase

An insertase is a membrane protein that facilitates the insertion and folding of other proteins into lipid membranes. Insertases act on proteins destined for insertion into membranes, guiding their hydrophobic segments into the lipid bilayer and, in many cases, helping to assemble multi-pass transmembrane proteins.

Most insertases function in coordination with other translocon complexes; in bacteria YidC can insert membrane proteins on its own or with SecYEG. The insertase recognizes hydrophobic transmembrane helices of substrate proteins, binds them, and promotes lateral integration into the lipid bilayer. Some insertases operate cotranslationally, engaging nascent chains as they emerge from ribosomes, while others act post-translationally.

The best-characterized family is the YidC/Oxa1/Alb3 family. In bacteria, YidC is essential and located in the inner membrane. In mitochondria, Oxa1 inserts proteins into the inner membrane, including a subset of mitochondrially encoded subunits and certain nuclear-encoded ones. In chloroplasts, Alb3 and related proteins perform similar tasks in the thylakoid membrane.

Insertases are central to assembly of respiratory chain complexes and photosynthetic apparatus, and defects in insertase function can disrupt membrane protein biogenesis. They can be integral to both Sec-dependent pathways and Sec-independent insertion, and represent a conserved mechanism for integrating hydrophobic proteins into membranes across life.