How quality control systems AID Sec-dependent protein translocation

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How quality control systems AID Sec-dependent protein translocation. / Jiang, Chen; Wynne, Max; Huber, Damon.

In: Frontiers in Molecular Bioscience, Vol. 8, 669376, 13.04.2021.

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@article{8c80f8d134504a928e7ee0df647f9219,
title = "How quality control systems AID Sec-dependent protein translocation",
abstract = "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.",
keywords = "Sec, molecular chaperones, proteases, protein targeting, protein translocation, quality control",
author = "Chen Jiang and Max Wynne and Damon Huber",
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: {\textcopyright} Copyright {\textcopyright} 2021 Jiang, Wynne and Huber.",
year = "2021",
month = apr,
day = "13",
doi = "10.3389/fmolb.2021.669376",
language = "English",
volume = "8",
journal = "Frontiers in Molecular Bioscience",
issn = "2296-889X",
publisher = "Frontiers Media",

}

RIS

TY - JOUR

T1 - How quality control systems AID Sec-dependent protein translocation

AU - Jiang, Chen

AU - Wynne, Max

AU - Huber, Damon

N1 - 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.

PY - 2021/4/13

Y1 - 2021/4/13

N2 - 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.

AB - 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.

KW - Sec

KW - molecular chaperones

KW - proteases

KW - protein targeting

KW - protein translocation

KW - quality control

UR - http://www.scopus.com/inward/record.url?scp=85104998909&partnerID=8YFLogxK

U2 - 10.3389/fmolb.2021.669376

DO - 10.3389/fmolb.2021.669376

M3 - Article

C2 - 33928127

VL - 8

JO - Frontiers in Molecular Bioscience

JF - Frontiers in Molecular Bioscience

SN - 2296-889X

M1 - 669376

ER -