A small single-domain protein folds through the same pathway on and off the ribosome

Guinn, Emily J.; Tian, Pengfei; Shin, Mia; Best, Robert B.; Marqusee, Susan

doi:10.1073/pnas.1810517115

A small single-domain protein folds through the same pathway on and off the ribosome

Journal Article · Thu Nov 08 00:00:00 EST 2018 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1810517115· OSTI ID:1561900

Guinn, Emily J. ^[1]; Tian, Pengfei ^[2]; Shin, Mia ^[3]; ^[2]; Marqusee, Susan ^[4]

Univ. of California, Berkeley, CA (United States). Inst. for Quantitative Biosciences (QB3)
National Inst. of Health (NIH), Bethesda, MD (United States). National Inst. of Diabetes and Digestive and Kidney Disease, Lab. of Chemical Physics
Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology
Univ. of California, Berkeley, CA (United States). Inst. for Quantitative Biosciences (QB3), Dept. of Molecular and Cell Biology, Dept. of Chemistry

In vivo, proteins fold and function in a complex environment subject to many stresses that can modulate a protein’s energy landscape. One aspect of the environment pertinent to protein folding is the ribosome, since proteins have the opportunity to fold while still bound to the ribosome during translation. We use a combination of force and chemical denaturant (chemomechanical unfolding), as well as point mutations, to characterize the folding mechanism of the src SH3 domain both as a stalled ribosome nascent chain and free in solution. Our results indicate that src SH3 folds through the same pathway on and off the ribosome. Molecular simulations also indicate that the ribosome does not affect the folding pathway for this small protein. Taken together, we conclude that the ribosome does not alter the folding mechanism of this small protein. These results, if general, suggest the ribosome may exert a bigger influence on the folding of multidomain proteins or protein domains that can partially fold before the entire domain sequence is outside the ribosome exit tunnel

View Accepted Manuscript (DOE)

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

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1561900

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 48 Vol. 115; ISSN 0027-8424

Publisher:: National Academy of Sciences, Washington, DC (United States)Copyright Statement

Country of Publication:: United States

Language:: English

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