Interactions between a subset of substrate side chains and AAA+ motor pore loops determine grip during protein unfolding
Most AAA+ remodeling motors denature proteins by pulling on the peptide termini of folded substrates, but it is not well-understood how motors produce grip when resisting a folded domain. Here, at single amino-acid resolution, we identify the determinants of grip by measuring how substrate tail sequ...
| Main Authors: | , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications, Ltd
2020
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| Online Access: | https://hdl.handle.net/1721.1/126161 |
| _version_ | 1826209629267296256 |
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| author | Bell, Tristan Andrew Baker, Tania Sauer, Robert T |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Bell, Tristan Andrew Baker, Tania Sauer, Robert T |
| author_sort | Bell, Tristan Andrew |
| collection | MIT |
| description | Most AAA+ remodeling motors denature proteins by pulling on the peptide termini of folded substrates, but it is not well-understood how motors produce grip when resisting a folded domain. Here, at single amino-acid resolution, we identify the determinants of grip by measuring how substrate tail sequences alter the unfolding activity of the unfoldase-protease ClpXP. The seven amino acids abutting a stable substrate domain are key, with residues 2-6 forming a core that contributes most significantly to grip. ClpX grips large hydrophobic and aromatic side chains strongly and small, polar, or charged side chains weakly. Multiple side chains interact with pore loops synergistically to strengthen grip. In combination with recent structures, our results support a mechanism in which unfolding grip is primarily mediated by non-specific van der Waal’s interactions between core side chains of the substrate tail and a subset of YVG loops at the top of the ClpX axial pore. |
| first_indexed | 2024-09-23T14:25:31Z |
| format | Article |
| id | mit-1721.1/126161 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:25:31Z |
| publishDate | 2020 |
| publisher | eLife Sciences Publications, Ltd |
| record_format | dspace |
| spelling | mit-1721.1/1261612022-09-29T09:24:42Z Interactions between a subset of substrate side chains and AAA+ motor pore loops determine grip during protein unfolding Bell, Tristan Andrew Baker, Tania Sauer, Robert T Massachusetts Institute of Technology. Department of Biology Most AAA+ remodeling motors denature proteins by pulling on the peptide termini of folded substrates, but it is not well-understood how motors produce grip when resisting a folded domain. Here, at single amino-acid resolution, we identify the determinants of grip by measuring how substrate tail sequences alter the unfolding activity of the unfoldase-protease ClpXP. The seven amino acids abutting a stable substrate domain are key, with residues 2-6 forming a core that contributes most significantly to grip. ClpX grips large hydrophobic and aromatic side chains strongly and small, polar, or charged side chains weakly. Multiple side chains interact with pore loops synergistically to strengthen grip. In combination with recent structures, our results support a mechanism in which unfolding grip is primarily mediated by non-specific van der Waal’s interactions between core side chains of the substrate tail and a subset of YVG loops at the top of the ClpX axial pore. National Institutes of Health (U.S.) (Grant GM-101988) National Institutes of Health (U.S.) (Grant 5T32GM-007287) 2020-07-13T18:39:48Z 2020-07-13T18:39:48Z 2019-06 2019-11-26T17:42:50Z Article http://purl.org/eprint/type/JournalArticle 1534-4983 https://hdl.handle.net/1721.1/126161 Bell, Tristan A., Tania A Baker and Robert T Sauer. “Interactions between a subset of substrate side chains and AAA+ motor pore loops determine grip during protein unfolding.” eLife, vol. 8, 2019, article e46808 © 2019 The Author(s) en 10.7554/ELIFE.46808 eLife Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf eLife Sciences Publications, Ltd eLife |
| spellingShingle | Bell, Tristan Andrew Baker, Tania Sauer, Robert T Interactions between a subset of substrate side chains and AAA+ motor pore loops determine grip during protein unfolding |
| title | Interactions between a subset of substrate side chains and AAA+ motor pore loops determine grip during protein unfolding |
| title_full | Interactions between a subset of substrate side chains and AAA+ motor pore loops determine grip during protein unfolding |
| title_fullStr | Interactions between a subset of substrate side chains and AAA+ motor pore loops determine grip during protein unfolding |
| title_full_unstemmed | Interactions between a subset of substrate side chains and AAA+ motor pore loops determine grip during protein unfolding |
| title_short | Interactions between a subset of substrate side chains and AAA+ motor pore loops determine grip during protein unfolding |
| title_sort | interactions between a subset of substrate side chains and aaa motor pore loops determine grip during protein unfolding |
| url | https://hdl.handle.net/1721.1/126161 |
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