The ClpS Adaptor Mediates Staged Delivery of N-End Rule Substrates to the AAA+ ClpAP Protease
The ClpS adaptor delivers N-end rule substrates to ClpAP, an energy-dependent AAA+ protease, for degradation. How ClpS binds specific N-end residues is known in atomic detail and clarified here, but the delivery mechanism is poorly understood. We show that substrate binding is enhanced when ClpS bin...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2014
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| Online Access: | http://hdl.handle.net/1721.1/84568 https://orcid.org/0000-0002-1719-5399 |
| _version_ | 1826199439198388224 |
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| author | Hou, Jennifer Y. Grant, Robert A. Roman-Hernandez, Giselle Baker, Tania |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Hou, Jennifer Y. Grant, Robert A. Roman-Hernandez, Giselle Baker, Tania |
| author_sort | Hou, Jennifer Y. |
| collection | MIT |
| description | The ClpS adaptor delivers N-end rule substrates to ClpAP, an energy-dependent AAA+ protease, for degradation. How ClpS binds specific N-end residues is known in atomic detail and clarified here, but the delivery mechanism is poorly understood. We show that substrate binding is enhanced when ClpS binds hexameric ClpA. Reciprocally, N-end rule substrates increase ClpS affinity for ClpA[subscript 6]. Enhanced binding requires the N-end residue and a peptide bond of the substrate, as well as multiple aspects of ClpS, including a side chain that contacts the substrate α-amino group and the flexible N-terminal extension (NTE). Finally, enhancement also needs the N domain and AAA+ rings of ClpA, connected by a long linker. The NTE can be engaged by the ClpA translocation pore, but ClpS resists unfolding/degradation. We propose a staged-delivery model that illustrates how intimate contacts between the substrate, adaptor, and protease reprogram specificity and coordinate handoff from the adaptor to the protease. |
| first_indexed | 2024-09-23T11:19:54Z |
| format | Article |
| id | mit-1721.1/84568 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:19:54Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/845682022-09-27T18:45:48Z The ClpS Adaptor Mediates Staged Delivery of N-End Rule Substrates to the AAA+ ClpAP Protease Hou, Jennifer Y. Grant, Robert A. Roman-Hernandez, Giselle Baker, Tania Massachusetts Institute of Technology. Department of Biology Roman-Hernandez, Giselle Hou, Jennifer Y. Grant, Robert A. Sauer, Robert T. Baker, Tania The ClpS adaptor delivers N-end rule substrates to ClpAP, an energy-dependent AAA+ protease, for degradation. How ClpS binds specific N-end residues is known in atomic detail and clarified here, but the delivery mechanism is poorly understood. We show that substrate binding is enhanced when ClpS binds hexameric ClpA. Reciprocally, N-end rule substrates increase ClpS affinity for ClpA[subscript 6]. Enhanced binding requires the N-end residue and a peptide bond of the substrate, as well as multiple aspects of ClpS, including a side chain that contacts the substrate α-amino group and the flexible N-terminal extension (NTE). Finally, enhancement also needs the N domain and AAA+ rings of ClpA, connected by a long linker. The NTE can be engaged by the ClpA translocation pore, but ClpS resists unfolding/degradation. We propose a staged-delivery model that illustrates how intimate contacts between the substrate, adaptor, and protease reprogram specificity and coordinate handoff from the adaptor to the protease. Howard Hughes Medical Institute National Institutes of Health (U.S.) (Grant AI-15706) National Institutes of Health (U.S.) (Grant AI-16892) National Institutes of Health (U.S.) (Grant GM-049224) 2014-01-27T16:21:55Z 2014-01-27T16:21:55Z 2011-07 2011-04 Article http://purl.org/eprint/type/JournalArticle 10972765 1097-4164 http://hdl.handle.net/1721.1/84568 Román-Hernández, Giselle, Jennifer Y. Hou, Robert A. Grant, Robert T. Sauer, and Tania A. Baker. “The ClpS Adaptor Mediates Staged Delivery of N-End Rule Substrates to the AAA+ ClpAP Protease.” Molecular Cell 43, no. 2 (July 2011): 217-228. Copyright © 2011 Elsevier Inc. https://orcid.org/0000-0002-1719-5399 en_US http://dx.doi.org/10.1016/j.molcel.2011.06.009 Molecular Cell 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 Elsevier Elsevier Open Archive |
| spellingShingle | Hou, Jennifer Y. Grant, Robert A. Roman-Hernandez, Giselle Baker, Tania The ClpS Adaptor Mediates Staged Delivery of N-End Rule Substrates to the AAA+ ClpAP Protease |
| title | The ClpS Adaptor Mediates Staged Delivery of N-End Rule Substrates to the AAA+ ClpAP Protease |
| title_full | The ClpS Adaptor Mediates Staged Delivery of N-End Rule Substrates to the AAA+ ClpAP Protease |
| title_fullStr | The ClpS Adaptor Mediates Staged Delivery of N-End Rule Substrates to the AAA+ ClpAP Protease |
| title_full_unstemmed | The ClpS Adaptor Mediates Staged Delivery of N-End Rule Substrates to the AAA+ ClpAP Protease |
| title_short | The ClpS Adaptor Mediates Staged Delivery of N-End Rule Substrates to the AAA+ ClpAP Protease |
| title_sort | clps adaptor mediates staged delivery of n end rule substrates to the aaa clpap protease |
| url | http://hdl.handle.net/1721.1/84568 https://orcid.org/0000-0002-1719-5399 |
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