Cryo-EM structures of the endoplasmic reticulum membrane complex

FEBS J. 2022 Jan;289(1):102-112. doi: 10.1111/febs.15786. Epub 2021 Mar 6.


The transmembrane α-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 α-helices are less hydrophobic and form membrane channels or substrate-binding pockets. Insertion of these amphipathic transmembrane α-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.

Keywords: Cryo-EM; insertase; membrane protein biogenesis; membrane protein folding; structural biology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cryoelectron Microscopy
  • Endoplasmic Reticulum / genetics
  • Endoplasmic Reticulum / ultrastructure*
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Intracellular Membranes / chemistry
  • Intracellular Membranes / ultrastructure*
  • Membrane Proteins / genetics
  • Membrane Proteins / ultrastructure*
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / ultrastructure*
  • Protein Transport / genetics
  • Saccharomyces cerevisiae / genetics


  • Membrane Proteins
  • Multiprotein Complexes