Degrons in Protein Substrates Program the Speed and Operating Efficiency of the AAA+ Lon Proteolytic Machine
AAA+ proteases are ATP-fueled machines that bind protein substrates via a degradation tag, unfold the molecule if necessary, and then translocate the polypeptide into a chamber for proteolysis. Tag recognition is normally viewed as a passive reaction. By contrast, for the AAA+ Lon protease, we show...
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2010
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| Online Access: | http://hdl.handle.net/1721.1/58301 https://orcid.org/0000-0002-1719-5399 |
| _version_ | 1826197189528911872 |
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| author | Gur, Eyal Sauer, Robert T |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Gur, Eyal Sauer, Robert T |
| author_sort | Gur, Eyal |
| collection | MIT |
| description | AAA+ proteases are ATP-fueled machines that bind protein substrates via a degradation tag, unfold the molecule if necessary, and then translocate the polypeptide into a chamber for proteolysis. Tag recognition is normally viewed as a passive reaction. By contrast, for the AAA+ Lon protease, we show that degron tags are also regulatory elements that determine protease activity levels. Indeed, different tags fused to the same protein change degradation speeds and energetic efficiencies by 10-fold or more. Degron binding to multiple sites in the Lon hexamer appears to differentially stabilize specific enzyme conformations, including one with high protease and low ATPase activity, and results in positively cooperative degradation. These allosteric mechanisms allow Lon to operate in either a fast or slow proteolysis mode, according to specific physiological needs, and may help maximize degradation of misfolded proteins following stress-induced denaturation. |
| first_indexed | 2024-09-23T10:44:11Z |
| format | Article |
| id | mit-1721.1/58301 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:44:11Z |
| publishDate | 2010 |
| publisher | National Academy of Sciences (U.S.) |
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| spelling | mit-1721.1/583012022-09-30T22:36:56Z Degrons in Protein Substrates Program the Speed and Operating Efficiency of the AAA+ Lon Proteolytic Machine Gur, Eyal Sauer, Robert T Massachusetts Institute of Technology. Department of Biology Sauer, Robert T. Sauer, Robert T. Gur, Eyal AAA+ protease Allosteric control Degradation tags AAA+ proteases are ATP-fueled machines that bind protein substrates via a degradation tag, unfold the molecule if necessary, and then translocate the polypeptide into a chamber for proteolysis. Tag recognition is normally viewed as a passive reaction. By contrast, for the AAA+ Lon protease, we show that degron tags are also regulatory elements that determine protease activity levels. Indeed, different tags fused to the same protein change degradation speeds and energetic efficiencies by 10-fold or more. Degron binding to multiple sites in the Lon hexamer appears to differentially stabilize specific enzyme conformations, including one with high protease and low ATPase activity, and results in positively cooperative degradation. These allosteric mechanisms allow Lon to operate in either a fast or slow proteolysis mode, according to specific physiological needs, and may help maximize degradation of misfolded proteins following stress-induced denaturation. National Institutes of Health (U.S.) (Grant AI-15706 and AI-16892) 2010-09-03T14:30:57Z 2010-09-03T14:30:57Z 2009-10 2009-08 Article http://purl.org/eprint/type/JournalArticle 0027-8424 http://hdl.handle.net/1721.1/58301 Eyal Gur and Robert T. Sauer, “Degrons in protein substrates program the speed and operating efficiency of the AAA+ Lon proteolytic machine,” Proceedings of the National Academy of Sciences 106, no. 44 (November 3, 2009): 18503 -18508. 19841274 https://orcid.org/0000-0002-1719-5399 en_US http://dx.doi.org/10.1073/pnas.0910392106 Proceedings of the National Academy of Sciences of the United States of America 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 National Academy of Sciences (U.S.) PNAS |
| spellingShingle | AAA+ protease Allosteric control Degradation tags Gur, Eyal Sauer, Robert T Degrons in Protein Substrates Program the Speed and Operating Efficiency of the AAA+ Lon Proteolytic Machine |
| title | Degrons in Protein Substrates Program the Speed and Operating Efficiency of the AAA+ Lon Proteolytic Machine |
| title_full | Degrons in Protein Substrates Program the Speed and Operating Efficiency of the AAA+ Lon Proteolytic Machine |
| title_fullStr | Degrons in Protein Substrates Program the Speed and Operating Efficiency of the AAA+ Lon Proteolytic Machine |
| title_full_unstemmed | Degrons in Protein Substrates Program the Speed and Operating Efficiency of the AAA+ Lon Proteolytic Machine |
| title_short | Degrons in Protein Substrates Program the Speed and Operating Efficiency of the AAA+ Lon Proteolytic Machine |
| title_sort | degrons in protein substrates program the speed and operating efficiency of the aaa lon proteolytic machine |
| topic | AAA+ protease Allosteric control Degradation tags |
| url | http://hdl.handle.net/1721.1/58301 https://orcid.org/0000-0002-1719-5399 |
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