Measuring protein stability in the GroEL chaperonin cage reveals massive destabilization
The thermodynamics of protein folding in bulk solution have been thoroughly investigated for decades. By contrast, measurements of protein substrate stability inside the GroEL/ES chaperonin cage have not been reported. Such measurements require stable encapsulation, that is no escape of the substrat...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-07-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/56511 |
| _version_ | 1811252886619815936 |
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| author | Ilia Korobko Hisham Mazal Gilad Haran Amnon Horovitz |
| author_facet | Ilia Korobko Hisham Mazal Gilad Haran Amnon Horovitz |
| author_sort | Ilia Korobko |
| collection | DOAJ |
| description | The thermodynamics of protein folding in bulk solution have been thoroughly investigated for decades. By contrast, measurements of protein substrate stability inside the GroEL/ES chaperonin cage have not been reported. Such measurements require stable encapsulation, that is no escape of the substrate into bulk solution during experiments, and a way to perturb protein stability without affecting the chaperonin system itself. Here, by establishing such conditions, we show that protein stability in the chaperonin cage is reduced dramatically by more than 5 kcal mol−1 compared to that in bulk solution. Given that steric confinement alone is stabilizing, our results indicate that hydrophobic and/or electrostatic effects in the cavity are strongly destabilizing. Our findings are consistent with the iterative annealing mechanism of action proposed for the chaperonin GroEL. |
| first_indexed | 2024-04-12T16:42:18Z |
| format | Article |
| id | doaj.art-58d49b94fa5f4f7cb176ed685ab9b668 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:42:18Z |
| publishDate | 2020-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-58d49b94fa5f4f7cb176ed685ab9b6682022-12-22T03:24:44ZengeLife Sciences Publications LtdeLife2050-084X2020-07-01910.7554/eLife.56511Measuring protein stability in the GroEL chaperonin cage reveals massive destabilizationIlia Korobko0Hisham Mazal1https://orcid.org/0000-0002-2071-9552Gilad Haran2https://orcid.org/0000-0003-1837-9779Amnon Horovitz3https://orcid.org/0000-0001-7952-6790Departments of Structural Biology, Weizmann Institute of Science, Rehovot, IsraelChemical and Biological Physics, Weizmann Institute of Science, Rehovot, IsraelChemical and Biological Physics, Weizmann Institute of Science, Rehovot, IsraelDepartments of Structural Biology, Weizmann Institute of Science, Rehovot, IsraelThe thermodynamics of protein folding in bulk solution have been thoroughly investigated for decades. By contrast, measurements of protein substrate stability inside the GroEL/ES chaperonin cage have not been reported. Such measurements require stable encapsulation, that is no escape of the substrate into bulk solution during experiments, and a way to perturb protein stability without affecting the chaperonin system itself. Here, by establishing such conditions, we show that protein stability in the chaperonin cage is reduced dramatically by more than 5 kcal mol−1 compared to that in bulk solution. Given that steric confinement alone is stabilizing, our results indicate that hydrophobic and/or electrostatic effects in the cavity are strongly destabilizing. Our findings are consistent with the iterative annealing mechanism of action proposed for the chaperonin GroEL.https://elifesciences.org/articles/56511chaperonesprotein foldingprotein stability |
| spellingShingle | Ilia Korobko Hisham Mazal Gilad Haran Amnon Horovitz Measuring protein stability in the GroEL chaperonin cage reveals massive destabilization eLife chaperones protein folding protein stability |
| title | Measuring protein stability in the GroEL chaperonin cage reveals massive destabilization |
| title_full | Measuring protein stability in the GroEL chaperonin cage reveals massive destabilization |
| title_fullStr | Measuring protein stability in the GroEL chaperonin cage reveals massive destabilization |
| title_full_unstemmed | Measuring protein stability in the GroEL chaperonin cage reveals massive destabilization |
| title_short | Measuring protein stability in the GroEL chaperonin cage reveals massive destabilization |
| title_sort | measuring protein stability in the groel chaperonin cage reveals massive destabilization |
| topic | chaperones protein folding protein stability |
| url | https://elifesciences.org/articles/56511 |
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