Mechanochemical basis of protein degradation by a double-ring AAA+ machine
Molecular machines containing double or single AAA+ rings power energy-dependent protein degradation and other critical cellular processes, including disaggregation and remodeling of macromolecular complexes. How the mechanical activities of double-ring and single-ring AAA+ enzymes differ is unknown...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2015
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| Online Access: | http://hdl.handle.net/1721.1/96709 https://orcid.org/0000-0003-1710-9582 https://orcid.org/0000-0002-1719-5399 |
| _version_ | 1811091574027714560 |
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| author | Iosefson, Ohad Olivares, Adrian O. Baker, Tania Nager, Andrew Ross Sauer, Robert T |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Iosefson, Ohad Olivares, Adrian O. Baker, Tania Nager, Andrew Ross Sauer, Robert T |
| author_sort | Iosefson, Ohad |
| collection | MIT |
| description | Molecular machines containing double or single AAA+ rings power energy-dependent protein degradation and other critical cellular processes, including disaggregation and remodeling of macromolecular complexes. How the mechanical activities of double-ring and single-ring AAA+ enzymes differ is unknown. Using single-molecule optical trapping, we determine how the double-ring ClpA enzyme from Escherichia coli, in complex with the ClpP peptidase, mechanically degrades proteins. We demonstrate that ClpA unfolds some protein substrates substantially faster than does the single-ring ClpX enzyme, which also degrades substrates in collaboration with ClpP. We find that ClpA is a slower polypeptide translocase and that it moves in physical steps that are smaller and more regular than steps taken by ClpX. These direct measurements of protein unfolding and translocation define the core mechanochemical behavior of a double-ring AAA+ machine and provide insight into the degradation of proteins that unfold via metastable intermediates. |
| first_indexed | 2024-09-23T15:04:32Z |
| format | Article |
| id | mit-1721.1/96709 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:04:32Z |
| publishDate | 2015 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/967092022-10-02T00:25:08Z Mechanochemical basis of protein degradation by a double-ring AAA+ machine Iosefson, Ohad Olivares, Adrian O. Baker, Tania Nager, Andrew Ross Sauer, Robert T Massachusetts Institute of Technology. Department of Biology Olivares, Adrian O. Sauer, Robert T. Baker, Tania Nager, Andrew Ross Iosefson, Ohad Molecular machines containing double or single AAA+ rings power energy-dependent protein degradation and other critical cellular processes, including disaggregation and remodeling of macromolecular complexes. How the mechanical activities of double-ring and single-ring AAA+ enzymes differ is unknown. Using single-molecule optical trapping, we determine how the double-ring ClpA enzyme from Escherichia coli, in complex with the ClpP peptidase, mechanically degrades proteins. We demonstrate that ClpA unfolds some protein substrates substantially faster than does the single-ring ClpX enzyme, which also degrades substrates in collaboration with ClpP. We find that ClpA is a slower polypeptide translocase and that it moves in physical steps that are smaller and more regular than steps taken by ClpX. These direct measurements of protein unfolding and translocation define the core mechanochemical behavior of a double-ring AAA+ machine and provide insight into the degradation of proteins that unfold via metastable intermediates. Howard Hughes Medical Institute National Institutes of Health (U.S.) (Grant AI-16892) 2015-04-22T18:35:38Z 2015-04-22T18:35:38Z 2014-09 2014-06 Article http://purl.org/eprint/type/JournalArticle 1545-9993 1545-9985 http://hdl.handle.net/1721.1/96709 Olivares, Adrian O, Andrew R Nager, Ohad Iosefson, Robert T Sauer, and Tania A Baker. “Mechanochemical Basis of Protein Degradation by a Double-Ring AAA+ Machine.” Nature Structural & Molecular Biology 21, no. 10 (September 7, 2014): 871–875. https://orcid.org/0000-0003-1710-9582 https://orcid.org/0000-0002-1719-5399 en_US http://dx.doi.org/10.1038/nsmb.2885 Nature Structural & Molecular Biology Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Nature Publishing Group PMC |
| spellingShingle | Iosefson, Ohad Olivares, Adrian O. Baker, Tania Nager, Andrew Ross Sauer, Robert T Mechanochemical basis of protein degradation by a double-ring AAA+ machine |
| title | Mechanochemical basis of protein degradation by a double-ring AAA+ machine |
| title_full | Mechanochemical basis of protein degradation by a double-ring AAA+ machine |
| title_fullStr | Mechanochemical basis of protein degradation by a double-ring AAA+ machine |
| title_full_unstemmed | Mechanochemical basis of protein degradation by a double-ring AAA+ machine |
| title_short | Mechanochemical basis of protein degradation by a double-ring AAA+ machine |
| title_sort | mechanochemical basis of protein degradation by a double ring aaa machine |
| url | http://hdl.handle.net/1721.1/96709 https://orcid.org/0000-0003-1710-9582 https://orcid.org/0000-0002-1719-5399 |
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