Structures of the ATP-fueled ClpXP proteolytic machine bound to protein substrate
© 2020, eLife Sciences Publications Ltd. All rights reserved. ClpXP is an ATP-dependent protease in which the ClpX AAA+ motor binds, unfolds, and translocates specific protein substrates into the degradation chamber of ClpP. We present cryo-EM studies of the E. coli enzyme that show how asymmetric h...
| 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/1721.1/136296 |
| _version_ | 1826209937433296896 |
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| author | Fei, Xue Bell, Tristan A Jenni, Simon Stinson, Benjamin M Baker, Tania A Harrison, Stephen C Sauer, Robert T |
| author_facet | Fei, Xue Bell, Tristan A Jenni, Simon Stinson, Benjamin M Baker, Tania A Harrison, Stephen C Sauer, Robert T |
| author_sort | Fei, Xue |
| collection | MIT |
| description | © 2020, eLife Sciences Publications Ltd. All rights reserved. ClpXP is an ATP-dependent protease in which the ClpX AAA+ motor binds, unfolds, and translocates specific protein substrates into the degradation chamber of ClpP. We present cryo-EM studies of the E. coli enzyme that show how asymmetric hexameric rings of ClpX bind symmetric heptameric rings of ClpP and interact with protein substrates. Subunits in the ClpX hexamer assume a spiral conformation and interact with two-residue segments of substrate in the axial channel, as observed for other AAA+ proteases and protein-remodeling machines. Strictly sequential models of ATP hydrolysis and a power stroke that moves two residues of the substrate per translocation step have been inferred from these structural features for other AAA+ unfoldases, but biochemical and single-molecule biophysical studies indicate that ClpXP operates by a probabilistic mechanism in which five to eight residues are translocated for each ATP hydrolyzed. We propose structure-based models that could account for the functional results. |
| first_indexed | 2024-09-23T14:36:22Z |
| format | Article |
| id | mit-1721.1/136296 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:36:22Z |
| publishDate | 2021 |
| publisher | eLife Sciences Publications, Ltd |
| record_format | dspace |
| spelling | mit-1721.1/1362962021-10-28T03:35:13Z Structures of the ATP-fueled ClpXP proteolytic machine bound to protein substrate Fei, Xue Bell, Tristan A Jenni, Simon Stinson, Benjamin M Baker, Tania A Harrison, Stephen C Sauer, Robert T © 2020, eLife Sciences Publications Ltd. All rights reserved. ClpXP is an ATP-dependent protease in which the ClpX AAA+ motor binds, unfolds, and translocates specific protein substrates into the degradation chamber of ClpP. We present cryo-EM studies of the E. coli enzyme that show how asymmetric hexameric rings of ClpX bind symmetric heptameric rings of ClpP and interact with protein substrates. Subunits in the ClpX hexamer assume a spiral conformation and interact with two-residue segments of substrate in the axial channel, as observed for other AAA+ proteases and protein-remodeling machines. Strictly sequential models of ATP hydrolysis and a power stroke that moves two residues of the substrate per translocation step have been inferred from these structural features for other AAA+ unfoldases, but biochemical and single-molecule biophysical studies indicate that ClpXP operates by a probabilistic mechanism in which five to eight residues are translocated for each ATP hydrolyzed. We propose structure-based models that could account for the functional results. 2021-10-27T20:34:46Z 2021-10-27T20:34:46Z 2020 2021-07-14T12:50:30Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/136296 en 10.7554/ELIFE.52774 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 Jenni, Simon Stinson, Benjamin M Baker, Tania A Harrison, Stephen C Sauer, Robert T Structures of the ATP-fueled ClpXP proteolytic machine bound to protein substrate |
| title | Structures of the ATP-fueled ClpXP proteolytic machine bound to protein substrate |
| title_full | Structures of the ATP-fueled ClpXP proteolytic machine bound to protein substrate |
| title_fullStr | Structures of the ATP-fueled ClpXP proteolytic machine bound to protein substrate |
| title_full_unstemmed | Structures of the ATP-fueled ClpXP proteolytic machine bound to protein substrate |
| title_short | Structures of the ATP-fueled ClpXP proteolytic machine bound to protein substrate |
| title_sort | structures of the atp fueled clpxp proteolytic machine bound to protein substrate |
| url | https://hdl.handle.net/1721.1/136296 |
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