Bipartite determinants mediate an evolutionarily conserved interaction between Cdc48 and the 20S peptidase
Proteasomes are essential and ubiquitous ATP-dependent proteases that function in eukarya, archaea, and some bacteria. These destructive but critically important proteolytic machines use a 20S core peptidase and a hexameric ATPase associated with a variety of cellular activities (AAA+) unfolding rin...
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2013
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| Online Access: | http://hdl.handle.net/1721.1/80398 https://orcid.org/0000-0002-1719-5399 |
| _version_ | 1826198648267997184 |
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| author | Barthelme, Dominik Sauer, Robert T |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Barthelme, Dominik Sauer, Robert T |
| author_sort | Barthelme, Dominik |
| collection | MIT |
| description | Proteasomes are essential and ubiquitous ATP-dependent proteases that function in eukarya, archaea, and some bacteria. These destructive but critically important proteolytic machines use a 20S core peptidase and a hexameric ATPase associated with a variety of cellular activities (AAA+) unfolding ring that unfolds and spools substrates into the peptidase chamber. In archaea, 20S can function with the AAA+ Cdc48 or proteasome-activating nucleotidase (PAN) unfoldases. Both interactions are stabilized by C-terminal tripeptides in AAA+ subunits that dock into pockets on the 20S periphery. Here, we provide evidence that archaeal Cdc48 also uses a distinct set of near-axial interactions to bind 20S and propose that similar dual determinants mediate PAN–20S interactions and Rpt[subscript 1–6]–20S interactions in the 26S proteasome. Current dogma holds that the Rpt[subscript 1–6] unfolding ring of the 19S regulatory particle is the only AAA+ partner of eukaryotic 20S. By contrast, we show that mammalian Cdc48, a key player in cell-cycle regulation, membrane fusion, and endoplasmic-reticulum–associated degradation, activates mammalian 20S and find that a mouse Cdc48 variant supports protein degradation in combination with 20S. Our results suggest that eukaryotic Cdc48 orthologs function directly with 20S to maintain intracellular protein quality control. |
| first_indexed | 2024-09-23T11:08:03Z |
| format | Article |
| id | mit-1721.1/80398 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:08:03Z |
| publishDate | 2013 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/803982022-10-01T01:28:05Z Bipartite determinants mediate an evolutionarily conserved interaction between Cdc48 and the 20S peptidase Barthelme, Dominik Sauer, Robert T Massachusetts Institute of Technology. Department of Biology Barthelme, Dominik Sauer, Robert T. Proteasomes are essential and ubiquitous ATP-dependent proteases that function in eukarya, archaea, and some bacteria. These destructive but critically important proteolytic machines use a 20S core peptidase and a hexameric ATPase associated with a variety of cellular activities (AAA+) unfolding ring that unfolds and spools substrates into the peptidase chamber. In archaea, 20S can function with the AAA+ Cdc48 or proteasome-activating nucleotidase (PAN) unfoldases. Both interactions are stabilized by C-terminal tripeptides in AAA+ subunits that dock into pockets on the 20S periphery. Here, we provide evidence that archaeal Cdc48 also uses a distinct set of near-axial interactions to bind 20S and propose that similar dual determinants mediate PAN–20S interactions and Rpt[subscript 1–6]–20S interactions in the 26S proteasome. Current dogma holds that the Rpt[subscript 1–6] unfolding ring of the 19S regulatory particle is the only AAA+ partner of eukaryotic 20S. By contrast, we show that mammalian Cdc48, a key player in cell-cycle regulation, membrane fusion, and endoplasmic-reticulum–associated degradation, activates mammalian 20S and find that a mouse Cdc48 variant supports protein degradation in combination with 20S. Our results suggest that eukaryotic Cdc48 orthologs function directly with 20S to maintain intracellular protein quality control. National Institutes of Health (U.S.) (Grant AI-16892) 2013-09-11T16:54:53Z 2013-09-11T16:54:53Z 2013-02 2013-01 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/80398 Barthelme, D., and R. T. Sauer. “Bipartite determinants mediate an evolutionarily conserved interaction between Cdc48 and the 20S peptidase.” Proceedings of the National Academy of Sciences 110, no. 9 (February 26, 2013): 3327-3332. https://orcid.org/0000-0002-1719-5399 en_US http://dx.doi.org/10.1073/pnas.1300408110 Proceedings of the National Academy of Sciences 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 | Barthelme, Dominik Sauer, Robert T Bipartite determinants mediate an evolutionarily conserved interaction between Cdc48 and the 20S peptidase |
| title | Bipartite determinants mediate an evolutionarily conserved interaction between Cdc48 and the 20S peptidase |
| title_full | Bipartite determinants mediate an evolutionarily conserved interaction between Cdc48 and the 20S peptidase |
| title_fullStr | Bipartite determinants mediate an evolutionarily conserved interaction between Cdc48 and the 20S peptidase |
| title_full_unstemmed | Bipartite determinants mediate an evolutionarily conserved interaction between Cdc48 and the 20S peptidase |
| title_short | Bipartite determinants mediate an evolutionarily conserved interaction between Cdc48 and the 20S peptidase |
| title_sort | bipartite determinants mediate an evolutionarily conserved interaction between cdc48 and the 20s peptidase |
| url | http://hdl.handle.net/1721.1/80398 https://orcid.org/0000-0002-1719-5399 |
| work_keys_str_mv | AT barthelmedominik bipartitedeterminantsmediateanevolutionarilyconservedinteractionbetweencdc48andthe20speptidase AT sauerrobertt bipartitedeterminantsmediateanevolutionarilyconservedinteractionbetweencdc48andthe20speptidase |