AAA+ protease-adaptor structures reveal altered conformations and ring specialization
<jats:title>Abstract</jats:title><jats:p>ClpAP, a two-ring AAA+ protease, degrades N-end-rule proteins bound by the ClpS adaptor. Here we present high-resolution cryo-EM structures of <jats:italic>Escherichia coli</jats:italic> ClpAPS complexes, showing how ClpA pore lo...
| Main Authors: | , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2022
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| Online Access: | https://hdl.handle.net/1721.1/146735 |
| _version_ | 1826191713673150464 |
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| author | Kim, Sora Fei, Xue Sauer, Robert T Baker, Tania A |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Kim, Sora Fei, Xue Sauer, Robert T Baker, Tania A |
| author_sort | Kim, Sora |
| collection | MIT |
| description | <jats:title>Abstract</jats:title><jats:p>ClpAP, a two-ring AAA+ protease, degrades N-end-rule proteins bound by the ClpS adaptor. Here we present high-resolution cryo-EM structures of <jats:italic>Escherichia coli</jats:italic> ClpAPS complexes, showing how ClpA pore loops interact with the ClpS N-terminal extension (NTE), which is normally intrinsically disordered. In two classes, the NTE is bound by a spiral of pore-1 and pore-2 loops in a manner similar to substrate-polypeptide binding by many AAA+ unfoldases. Kinetic studies reveal that pore-2 loops of the ClpA D1 ring catalyze the protein remodeling required for substrate delivery by ClpS. In a third class, D2 pore-1 loops are rotated, tucked away from the channel and do not bind the NTE, demonstrating asymmetry in engagement by the D1 and D2 rings. These studies show additional structures and functions for key AAA+ elements. Pore-loop tucking may be used broadly by AAA+ unfoldases, for example, during enzyme pausing/unloading.</jats:p> |
| first_indexed | 2024-09-23T09:00:13Z |
| format | Article |
| id | mit-1721.1/146735 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:00:13Z |
| publishDate | 2022 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1467352022-12-03T03:41:40Z AAA+ protease-adaptor structures reveal altered conformations and ring specialization Kim, Sora Fei, Xue Sauer, Robert T Baker, Tania A Massachusetts Institute of Technology. Department of Biology <jats:title>Abstract</jats:title><jats:p>ClpAP, a two-ring AAA+ protease, degrades N-end-rule proteins bound by the ClpS adaptor. Here we present high-resolution cryo-EM structures of <jats:italic>Escherichia coli</jats:italic> ClpAPS complexes, showing how ClpA pore loops interact with the ClpS N-terminal extension (NTE), which is normally intrinsically disordered. In two classes, the NTE is bound by a spiral of pore-1 and pore-2 loops in a manner similar to substrate-polypeptide binding by many AAA+ unfoldases. Kinetic studies reveal that pore-2 loops of the ClpA D1 ring catalyze the protein remodeling required for substrate delivery by ClpS. In a third class, D2 pore-1 loops are rotated, tucked away from the channel and do not bind the NTE, demonstrating asymmetry in engagement by the D1 and D2 rings. These studies show additional structures and functions for key AAA+ elements. Pore-loop tucking may be used broadly by AAA+ unfoldases, for example, during enzyme pausing/unloading.</jats:p> 2022-12-02T14:30:49Z 2022-12-02T14:30:49Z 2022-11 2022-12-01T18:49:20Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/146735 Kim, Sora, Fei, Xue, Sauer, Robert T and Baker, Tania A. 2022. "AAA+ protease-adaptor structures reveal altered conformations and ring specialization." Nature Structural & Molecular Biology, 29 (11). en 10.1038/s41594-022-00850-3 Nature Structural & Molecular Biology Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature |
| spellingShingle | Kim, Sora Fei, Xue Sauer, Robert T Baker, Tania A AAA+ protease-adaptor structures reveal altered conformations and ring specialization |
| title | AAA+ protease-adaptor structures reveal altered conformations and ring specialization |
| title_full | AAA+ protease-adaptor structures reveal altered conformations and ring specialization |
| title_fullStr | AAA+ protease-adaptor structures reveal altered conformations and ring specialization |
| title_full_unstemmed | AAA+ protease-adaptor structures reveal altered conformations and ring specialization |
| title_short | AAA+ protease-adaptor structures reveal altered conformations and ring specialization |
| title_sort | aaa protease adaptor structures reveal altered conformations and ring specialization |
| url | https://hdl.handle.net/1721.1/146735 |
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