How quality control systems AID Sec-dependent protein translocation

Chen Jiang, Max Wynne, Damon Huber

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The evolutionarily conserved Sec machinery is responsible for transporting proteins across the cytoplasmic membrane. Protein substrates of the Sec machinery must be in an unfolded conformation in order to be translocated across (or inserted into) the cytoplasmic membrane. In bacteria, the requirement for unfolded proteins is strict: substrate proteins that fold (or misfold) prematurely in the cytoplasm prior to translocation become irreversibly trapped in the cytoplasm. Partially folded Sec substrate proteins and stalled ribosomes containing nascent Sec substrates can also inhibit translocation by blocking (i.e., “jamming”) the membrane-embedded Sec machinery. To avoid these issues, bacteria have evolved a complex network of quality control systems to ensure that Sec substrate proteins do not fold in the cytoplasm. This quality control network can be broken into three branches, for which we have defined the acronym “AID”: (i) avoidance of cytoplasmic intermediates through cotranslationally channeling newly synthesized Sec substrates to the Sec machinery; (ii) inhibition of folding Sec substrate proteins that transiently reside in the cytoplasm by molecular chaperones and the requirement for posttranslational modifications; (iii) destruction of products that could potentially inhibit translocation. In addition, several stress response pathways help to restore protein-folding homeostasis when environmental conditions that inhibit translocation overcome the AID quality control systems.
Original languageEnglish
Article number669376
Number of pages13
JournalFrontiers in Molecular Bioscience
Publication statusPublished - 13 Apr 2021

Bibliographical note

Funding Information:
We thank G. Williams and the members of the Huber lab for thoughtful discussions and feedback. Funding. MW was funded by the Biotechnology and Biological Sciences Research Council (BBSRC)-funded Midlands Integrative Biosciences Training Partnership (MIBTP).

Publisher Copyright:
© Copyright © 2021 Jiang, Wynne and Huber.


  • Sec
  • molecular chaperones
  • proteases
  • protein targeting
  • protein translocation
  • quality control

ASJC Scopus subject areas

  • Biochemistry
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Molecular Biology


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