Structural basis of ClpXP recognition and unfolding of ssrA-tagged substrates
© 2020, eLife Sciences Publications Ltd. All rights reserved. When ribosomes fail to complete normal translation, all cells have mechanisms to ensure degradation of the resulting partial proteins to safeguard proteome integrity. In E. coli and other eubacteria, the tmRNA system rescues stalled ribos...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications, Ltd
2021
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| Online Access: | https://hdl.handle.net/1721.1/135281 |
| _version_ | 1826188804252237824 |
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| author | Fei, Xue Bell, Tristan A Barkow, Sarah R Baker, Tania A Sauer, Robert T |
| author_facet | Fei, Xue Bell, Tristan A Barkow, Sarah R Baker, Tania A Sauer, Robert T |
| author_sort | Fei, Xue |
| collection | MIT |
| description | © 2020, eLife Sciences Publications Ltd. All rights reserved. When ribosomes fail to complete normal translation, all cells have mechanisms to ensure degradation of the resulting partial proteins to safeguard proteome integrity. In E. coli and other eubacteria, the tmRNA system rescues stalled ribosomes and adds an ssrA tag or degron to the C-terminus of the incomplete protein, which directs degradation by the AAA+ ClpXP protease. Here, we present cryo-EM structures of ClpXP bound to the ssrA degron. C-terminal residues of the ssrA degron initially bind in the top of an otherwise closed ClpX axial channel and subsequently move deeper into an open channel. For short-degron protein substrates, we show that unfolding can occur directly from the initial closed-channel complex. For longer-degron substrates, our studies illuminate how ClpXP transitions from specific recognition into a nonspecific unfolding and translocation machine. Many AAA+ proteases and protein-remodeling motors are likely to employ similar multistep recognition and engagement strategies. |
| first_indexed | 2024-09-23T08:04:58Z |
| format | Article |
| id | mit-1721.1/135281 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T08:04:58Z |
| publishDate | 2021 |
| publisher | eLife Sciences Publications, Ltd |
| record_format | dspace |
| spelling | mit-1721.1/1352812021-10-28T05:03:37Z Structural basis of ClpXP recognition and unfolding of ssrA-tagged substrates Fei, Xue Bell, Tristan A Barkow, Sarah R Baker, Tania A Sauer, Robert T © 2020, eLife Sciences Publications Ltd. All rights reserved. When ribosomes fail to complete normal translation, all cells have mechanisms to ensure degradation of the resulting partial proteins to safeguard proteome integrity. In E. coli and other eubacteria, the tmRNA system rescues stalled ribosomes and adds an ssrA tag or degron to the C-terminus of the incomplete protein, which directs degradation by the AAA+ ClpXP protease. Here, we present cryo-EM structures of ClpXP bound to the ssrA degron. C-terminal residues of the ssrA degron initially bind in the top of an otherwise closed ClpX axial channel and subsequently move deeper into an open channel. For short-degron protein substrates, we show that unfolding can occur directly from the initial closed-channel complex. For longer-degron substrates, our studies illuminate how ClpXP transitions from specific recognition into a nonspecific unfolding and translocation machine. Many AAA+ proteases and protein-remodeling motors are likely to employ similar multistep recognition and engagement strategies. 2021-10-27T20:22:46Z 2021-10-27T20:22:46Z 2020 2021-07-14T12:48:18Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135281 en 10.7554/ELIFE.61496 eLife Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf eLife Sciences Publications, Ltd eLife |
| spellingShingle | Fei, Xue Bell, Tristan A Barkow, Sarah R Baker, Tania A Sauer, Robert T Structural basis of ClpXP recognition and unfolding of ssrA-tagged substrates |
| title | Structural basis of ClpXP recognition and unfolding of ssrA-tagged substrates |
| title_full | Structural basis of ClpXP recognition and unfolding of ssrA-tagged substrates |
| title_fullStr | Structural basis of ClpXP recognition and unfolding of ssrA-tagged substrates |
| title_full_unstemmed | Structural basis of ClpXP recognition and unfolding of ssrA-tagged substrates |
| title_short | Structural basis of ClpXP recognition and unfolding of ssrA-tagged substrates |
| title_sort | structural basis of clpxp recognition and unfolding of ssra tagged substrates |
| url | https://hdl.handle.net/1721.1/135281 |
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