The ER membrane protein complex interacts cotranslationally to enable biogenesis of multipass membrane proteins

Elife. 2018 May 29;7:e37018. doi: 10.7554/eLife.37018.

Abstract

The endoplasmic reticulum (ER) supports biosynthesis of proteins with diverse transmembrane domain (TMD) lengths and hydrophobicity. Features in transmembrane domains such as charged residues in ion channels are often functionally important, but could pose a challenge during cotranslational membrane insertion and folding. Our systematic proteomic approaches in both yeast and human cells revealed that the ER membrane protein complex (EMC) binds to and promotes the biogenesis of a range of multipass transmembrane proteins, with a particular enrichment for transporters. Proximity-specific ribosome profiling demonstrates that the EMC engages clients cotranslationally and immediately following clusters of TMDs enriched for charged residues. The EMC can remain associated after completion of translation, which both protects clients from premature degradation and allows recruitment of substrate-specific and general chaperones. Thus, the EMC broadly enables the biogenesis of multipass transmembrane proteins containing destabilizing features, thereby mitigating the trade-off between function and stability.

Keywords: EMC; cell biology; endoplasmic reticulum; human; ion channel; transmembrane; transporter.

Publication types

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

MeSH terms

  • Endoplasmic Reticulum / metabolism*
  • Humans
  • Membrane Proteins / metabolism*
  • Molecular Chaperones / metabolism
  • Multiprotein Complexes / metabolism
  • Protein Biosynthesis*
  • Protein Transport
  • Proteomics
  • Ribosomes / metabolism
  • Saccharomyces cerevisiae / metabolism*

Substances

  • Membrane Proteins
  • Molecular Chaperones
  • Multiprotein Complexes