4.6 Review

Membrane translocation of folded proteins

Journal

JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 298, Issue 7, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.jbc.2022.102107

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Funding

  1. National Institutes of Health [GM122459, CA234124]
  2. National Sci-ence Foundation [MCB-1814936]

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This article provides an overview of systems and processes involved in the membrane translocation of folded proteins. It discusses various mechanisms for protein translocation, including pore/channel formation, local membrane disruption, membrane thinning, and transport by membrane vesicles. The article also introduces a newly discovered vesicular transport mechanism, vesicle budding and collapse, as a potential unifying mechanism for folded protein translocation processes.
An ever-increasing number of proteins have been shown to translocate across various membranes of bacterial as well as eukaryotic cells in their folded states as a part of physiological and/or pathophysiological processes. Herein, we provide an overview of the systems/processes that are established or likely to involve the membrane translocation of folded proteins, such as protein export by the twin-arginine translocation system in bacteria and chloroplasts, unconventional protein secretion and protein import into the peroxisome in eukaryotes, and the cytosolic entry of proteins (e.g., bacterial toxins) and viruses into eukaryotes. We also discuss the various mechanistic models that have previously been proposed for the membrane translocation of folded proteins including pore/channel formation, local membrane disruption, membrane thinning, and transport by membrane vesicles. Finally, we introduce a newly discovered vesicular transport mechanism, vesicle budding and collapse, and present evidence that vesicle budding and collapse may represent a unifying mechanism that drives some (and potentially all) of folded protein translocation processes.

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