Non-equilibrium dynamics of a nascent polypeptide during translation suppress its misfolding

Alexander, Lisa M.; Goldman, Daniel H.; Wee, Liang M.; Bustamante, Carlos

doi:10.1038/s41467-019-10647-6

Non-equilibrium dynamics of a nascent polypeptide during translation suppress its misfolding

Journal Article · Thu Jun 20 00:00:00 EDT 2019 · Nature Communications

DOI:https://doi.org/10.1038/s41467-019-10647-6· OSTI ID:1559262

Alexander, Lisa M. ^[1]; Goldman, Daniel H. ^[1]; Wee, Liang M. ^[2]; Bustamante, Carlos ^[3]

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)

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.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1559262

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 10; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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