Non-equilibrium dynamics of a nascent polypeptide during translation suppress its misfolding
Abstract
Protein folding can begin co-translationally. Due to the difference in timescale between folding and synthesis, co-translational folding is thought to occur at equilibrium for fastfolding domains. In this scenario, the folding kinetics of stalled ribosome-bound nascent chains should match the folding of nascent chains in real time. To test if this assumption is true, we compare the folding of a ribosome-bound, multi-domain calcium-binding protein stalled at different points in translation with the nascent chain as is it being synthesized in real-time, via optical tweezers. On stalled ribosomes, a misfolded state forms rapidly (1.5 s). However, during translation, this state is only attained after a long delay (63 s), indicating that, unexpectedly, the growing polypeptide is not equilibrated with its ensemble of accessible conformations. Slow equilibration on the ribosome can delay premature folding until adequate sequence is available and/or allow time for chaperone binding, thus promoting productive folding.
- Authors:
-
- Univ. of California, Berkeley, CA (United States). Dept. of Chemistry
- Univ. of California, Berkeley, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States); Johns Hopkins Univ., Baltimore, MD (United States)
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES)
- OSTI Identifier:
- 1559262
- Grant/Contract Number:
- AC02-05CH11231
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nature Communications
- Additional Journal Information:
- Journal Volume: 10; Journal Issue: 1; Journal ID: ISSN 2041-1723
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Alexander, Lisa M., Goldman, Daniel H., Wee, Liang M., and Bustamante, Carlos. Non-equilibrium dynamics of a nascent polypeptide during translation suppress its misfolding. United States: N. p., 2019.
Web. doi:10.1038/s41467-019-10647-6.
Alexander, Lisa M., Goldman, Daniel H., Wee, Liang M., & Bustamante, Carlos. Non-equilibrium dynamics of a nascent polypeptide during translation suppress its misfolding. United States. https://doi.org/10.1038/s41467-019-10647-6
Alexander, Lisa M., Goldman, Daniel H., Wee, Liang M., and Bustamante, Carlos. Thu .
"Non-equilibrium dynamics of a nascent polypeptide during translation suppress its misfolding". United States. https://doi.org/10.1038/s41467-019-10647-6. https://www.osti.gov/servlets/purl/1559262.
@article{osti_1559262,
title = {Non-equilibrium dynamics of a nascent polypeptide during translation suppress its misfolding},
author = {Alexander, Lisa M. and Goldman, Daniel H. and Wee, Liang M. and Bustamante, Carlos},
abstractNote = {Protein folding can begin co-translationally. Due to the difference in timescale between folding and synthesis, co-translational folding is thought to occur at equilibrium for fastfolding domains. In this scenario, the folding kinetics of stalled ribosome-bound nascent chains should match the folding of nascent chains in real time. To test if this assumption is true, we compare the folding of a ribosome-bound, multi-domain calcium-binding protein stalled at different points in translation with the nascent chain as is it being synthesized in real-time, via optical tweezers. On stalled ribosomes, a misfolded state forms rapidly (1.5 s). However, during translation, this state is only attained after a long delay (63 s), indicating that, unexpectedly, the growing polypeptide is not equilibrated with its ensemble of accessible conformations. Slow equilibration on the ribosome can delay premature folding until adequate sequence is available and/or allow time for chaperone binding, thus promoting productive folding.},
doi = {10.1038/s41467-019-10647-6},
journal = {Nature Communications},
number = 1,
volume = 10,
place = {United States},
year = {2019},
month = {6}
}
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