Dynamic and static components power unfolding in topologically closed rings of a AAA+ proteolytic machine
In the Escherichia coli ClpXP protease, a hexameric ClpX ring couples ATP binding and hydrolysis to mechanical protein unfolding and translocation into the ClpP degradation chamber. Rigid-body packing between the small AAA+ domain of each ClpX subunit and the large AAA+ domain of its neighbor stabil...
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2014
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| Online Access: | http://hdl.handle.net/1721.1/83605 https://orcid.org/0000-0002-1719-5399 |
| _version_ | 1826190538587504640 |
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| author | Glynn, Steven E. Nager, Andrew Ross Baker, Tania Sauer, Robert T |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Glynn, Steven E. Nager, Andrew Ross Baker, Tania Sauer, Robert T |
| author_sort | Glynn, Steven E. |
| collection | MIT |
| description | In the Escherichia coli ClpXP protease, a hexameric ClpX ring couples ATP binding and hydrolysis to mechanical protein unfolding and translocation into the ClpP degradation chamber. Rigid-body packing between the small AAA+ domain of each ClpX subunit and the large AAA+ domain of its neighbor stabilizes the hexamer. By connecting the parts of each rigid-body unit with disulfide bonds or linkers, we created covalently closed rings that retained robust activity. A single-residue insertion in the hinge that connects the large and small AAA+ domains and forms part of the nucleotide-binding site uncoupled ATP hydrolysis from productive unfolding. We propose that ATP hydrolysis drives changes in the conformation of one hinge and its flanking domains and that the changes are propagated around the AAA+ ring through the topologically constrained set of rigid-body units and hinges to produce coupled ring motions that power substrate unfolding. |
| first_indexed | 2024-09-23T08:41:47Z |
| format | Article |
| id | mit-1721.1/83605 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:41:47Z |
| publishDate | 2014 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/836052022-07-09T06:40:35Z Dynamic and static components power unfolding in topologically closed rings of a AAA+ proteolytic machine Glynn, Steven E. Nager, Andrew Ross Baker, Tania Sauer, Robert T Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Glynn, Steven E. Nager, Andrew Ross Baker, Tania Sauer, Robert T. In the Escherichia coli ClpXP protease, a hexameric ClpX ring couples ATP binding and hydrolysis to mechanical protein unfolding and translocation into the ClpP degradation chamber. Rigid-body packing between the small AAA+ domain of each ClpX subunit and the large AAA+ domain of its neighbor stabilizes the hexamer. By connecting the parts of each rigid-body unit with disulfide bonds or linkers, we created covalently closed rings that retained robust activity. A single-residue insertion in the hinge that connects the large and small AAA+ domains and forms part of the nucleotide-binding site uncoupled ATP hydrolysis from productive unfolding. We propose that ATP hydrolysis drives changes in the conformation of one hinge and its flanking domains and that the changes are propagated around the AAA+ ring through the topologically constrained set of rigid-body units and hinges to produce coupled ring motions that power substrate unfolding. National Institutes of Health (U.S.) (grant AI-15706) 2014-01-08T19:07:21Z 2014-01-08T19:07:21Z 2012-05 2012-01 Article http://purl.org/eprint/type/JournalArticle 1545-9993 1545-9985 http://hdl.handle.net/1721.1/83605 Glynn, Steven E, Andrew R Nager, Tania A Baker, and Robert T Sauer. “Dynamic and static components power unfolding in topologically closed rings of a AAA+ proteolytic machine.” Nature Structural & Molecular Biology 19, no. 6 (May 6, 2012): 616-622. https://orcid.org/0000-0002-1719-5399 en_US http://dx.doi.org/10.1038/nsmb.2288 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 | Glynn, Steven E. Nager, Andrew Ross Baker, Tania Sauer, Robert T Dynamic and static components power unfolding in topologically closed rings of a AAA+ proteolytic machine |
| title | Dynamic and static components power unfolding in topologically closed rings of a AAA+ proteolytic machine |
| title_full | Dynamic and static components power unfolding in topologically closed rings of a AAA+ proteolytic machine |
| title_fullStr | Dynamic and static components power unfolding in topologically closed rings of a AAA+ proteolytic machine |
| title_full_unstemmed | Dynamic and static components power unfolding in topologically closed rings of a AAA+ proteolytic machine |
| title_short | Dynamic and static components power unfolding in topologically closed rings of a AAA+ proteolytic machine |
| title_sort | dynamic and static components power unfolding in topologically closed rings of a aaa proteolytic machine |
| url | http://hdl.handle.net/1721.1/83605 https://orcid.org/0000-0002-1719-5399 |
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