Fig. 7: The EMC acts as a chaperone for membrane proteins.

The chaperone site of the EMC recognizes transmembrane domains bearing suboptimal features, e.g. polar residues, which are often only marginally stable inside the lipid bilayer. Hydrophobic interactions with the EMC1 transmembrane domain stabilize and reorient these TMDs inside the membrane until assembly with a cognate partner occurs, which makes EMC binding no longer necessary and thus leads to release. The correctly folded and assembled membrane protein is no longer retained in the ER and can traffic to the cell surface. Note that the depicted processes are likely influenced and/or coupled to TMD insertion into the lipid bilayer.