Translocation of Proteins through a Distorted Lipid Bilayer

Trends Cell Biol. 2021 Jun;31(6):473-484. doi: 10.1016/j.tcb.2021.01.002. Epub 2021 Jan 30.


Membranes surrounding cells or organelles represent barriers to proteins and other molecules. However, specific proteins can cross membranes by different translocation systems, the best studied being the Sec61/SecY channel. This channel forms a hydrophilic, hourglass-shaped membrane channel, with a lateral gate towards the surrounding lipid. However, recent studies show that an aqueous pore is not required in other cases of protein translocation. The Hrd1 complex, mediating the retrotranslocation of misfolded proteins from the endoplasmic reticulum (ER) lumen into the cytosol, contains multispanning proteins with aqueous luminal and cytosolic cavities, and lateral gates juxtaposed in a thinned membrane region. A locally thinned, distorted lipid bilayer also allows protein translocation in other systems, suggesting a new paradigm to overcome the membrane barrier.

Keywords: endoplasmic reticulum; lipid bilayer; membrane distortion; protein translocation; structure.

Publication types

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

MeSH terms

  • Endoplasmic Reticulum / metabolism
  • Endoplasmic Reticulum-Associated Degradation
  • Lipid Bilayers* / metabolism
  • Protein Transport
  • Saccharomyces cerevisiae Proteins* / metabolism


  • Lipid Bilayers
  • Saccharomyces cerevisiae Proteins