Cryo-EM structures of the endoplasmic reticulum membrane complex

The transmembrane alpha-helices of membrane proteins are in general highly hydrophobic, and they enter the lipid bilayer through a lateral gate in the Sec61 translocon. However, some transmembrane alpha-helices are less hydrophobic and form membrane channels or substrate-binding pockets. Insertion of these amphipathic transmembrane alpha-helices into the membrane requires the specific membrane-embedded insertase called the endoplasmic reticulum membrane complex (EMC), which is a multi-subunit chaperone distinct from the GET insertase complex. Four recent cryo-electron microscopy studies on the eukaryotic EMC have revealed their remarkable architectural conservation from yeast to humans; a general consensus on the substrate transmembrane helix-binding pocket; and the evolutionary link to the prokaryotic insertases of the tail-anchored membrane proteins. These structures provide a solid framework for future mechanistic investigation.

Automated summary

Membrane proteins' transmembrane alpha-helices come in highly hydrophobic and less hydrophobic forms, with insertion into the membrane requiring different insertase enzymes. Recent cryo-electron microscopy studies have shown structural conservation of the endoplasmic reticulum membrane complex (EMC) from yeast to humans, a common substrate-binding pocket, and evolutionary similarities to prokaryotic insertases. These findings offer a foundation for future mechanistic research.