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Translocation of Proteins through a Distorted Lipid Bilayer

Journal

TRENDS IN CELL BIOLOGY
Volume 31, Issue 6, Pages 473-484

Publisher

CELL PRESS
DOI: 10.1016/j.tcb.2021.01.002

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Funding

  1. Jane Coffin Child fellowship
  2. National Institute of General Medical Sciences (NIGMS) [R01GM052586]

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The membranes surrounding cells or organelles act as barriers for proteins and molecules, but certain proteins can cross through different translocation systems. Recent studies show that in some cases, an aqueous pore is not necessary for protein translocation to occur.
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.

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