A small single-domain protein folds through the same pathway on- and off- the ribosome
| Autor: | Emily J. Guinn, Robert B. Best, Susan Marqusee, Mia Shin, Pengfei Tian |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Protein Folding 1.1 Normal biological development and functioning 030303 biophysics Protein domain Molecular Dynamics Simulation Ribosome single-molecule force spectroscopy SH3 domain 03 medical and health sciences Protein Domains Underpinning research MD Multidisciplinary Protein biosynthesis Single domain 030304 developmental biology 0303 health sciences Multidisciplinary 030102 biochemistry & molecular biology optical tweezers Chemistry Point mutation Energy landscape Proteins Fold (geology) Biological Sciences 030104 developmental biology ribosome Protein Biosynthesis Biophysics cotranslational folding Protein folding Generic health relevance Ribosomes Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America, vol 115, iss 48 |
| DOI: | 10.1101/347864 |
| Popis: | In vivo, proteins fold and function in a complex environment where they are subject to many stresses that can modulate protein energy landscapes. 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 (chemo-mechanical 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, which appears to fold at the mouth of the ribosome as the protein emerges from the exit tunnel. These results, if general, suggest the ribosome may exert a bigger influence on the folding of multi-domain proteins or protein domains that can partially fold before the entire domain sequence is outside the ribosome exit tunnel. |
| Databáze: | OpenAIRE |
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