Cryo‐EM structures of the endoplasmic reticulum membrane complex

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...

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Bibliographic Details
Published in:The FEBS journal 2022-01, Vol.289 (1), p.102-112
Main Authors: Bai, Lin, Li, Huilin
Format: Article
Language:English
Subjects:
Binding
Cryoelectron Microscopy
Cryo‐EM
Electron microscopy
Endoplasmic reticulum
Endoplasmic Reticulum - genetics
Endoplasmic Reticulum - ultrastructure
Helices
Humans
Hydrophobic and Hydrophilic Interactions
Hydrophobicity
insertase
Intracellular Membranes - chemistry
Intracellular Membranes - ultrastructure
Lipid bilayers
Lipids
Membrane channels
membrane protein biogenesis
membrane protein folding
Membrane proteins
Membrane Proteins - genetics
Membrane Proteins - ultrastructure
Membranes
Multiprotein Complexes - genetics
Multiprotein Complexes - ultrastructure
Protein Transport - genetics
Proteins
Saccharomyces cerevisiae - genetics
structural biology
Substrates
Yeasts
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Summary: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. ER membrane complex (EMC) has eight subunits in yeast and nine in humans. EMC is a dual‐function complex that inserts transmembrane domain of the tail‐anchored proteins and chaperones biogenesis of multipass transmembrane proteins containing partially hydrophilic transmembrane helices. The EMC insertase and holdase activities are separable. The EMC structure contains two sizable cavities—a gated partially hydrophilic cavity and a lipid‐filled hydrophobic cavity. Both cavities are involved in the EMC functions.
ISSN:1742-464X
1742-4658
DOI:10.1111/febs.15786