Cargando…
A Single α Helix Drives Extensive Remodeling of the Proteasome Lid and Completion of Regulatory Particle Assembly
Most short-lived eukaryotic proteins are degraded by the proteasome. A proteolytic core particle (CP) capped by regulatory particles (RPs) constitutes the 26S proteasome complex. RP biogenesis culminates with the joining of two large subcomplexes, the lid and base. In yeast and mammals, the lid appe...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601081/ https://www.ncbi.nlm.nih.gov/pubmed/26451487 http://dx.doi.org/10.1016/j.cell.2015.09.022 |
_version_ | 1782394507778588672 |
---|---|
author | Tomko, Robert J. Taylor, David W. Chen, Zhuo A. Wang, Hong-Wei Rappsilber, Juri Hochstrasser, Mark |
author_facet | Tomko, Robert J. Taylor, David W. Chen, Zhuo A. Wang, Hong-Wei Rappsilber, Juri Hochstrasser, Mark |
author_sort | Tomko, Robert J. |
collection | PubMed |
description | Most short-lived eukaryotic proteins are degraded by the proteasome. A proteolytic core particle (CP) capped by regulatory particles (RPs) constitutes the 26S proteasome complex. RP biogenesis culminates with the joining of two large subcomplexes, the lid and base. In yeast and mammals, the lid appears to assemble completely before attaching to the base, but how this hierarchical assembly is enforced has remained unclear. Using biochemical reconstitutions, quantitative cross-linking/mass spectrometry, and electron microscopy, we resolve the mechanistic basis for the linkage between lid biogenesis and lid-base joining. Assimilation of the final lid subunit, Rpn12, triggers a large-scale conformational remodeling of the nascent lid that drives RP assembly, in part by relieving steric clash with the base. Surprisingly, this remodeling is triggered by a single Rpn12 α helix. Such assembly-coupled conformational switching is reminiscent of viral particle maturation and may represent a commonly used mechanism to enforce hierarchical assembly in multisubunit complexes. |
format | Online Article Text |
id | pubmed-4601081 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-46010812015-10-28 A Single α Helix Drives Extensive Remodeling of the Proteasome Lid and Completion of Regulatory Particle Assembly Tomko, Robert J. Taylor, David W. Chen, Zhuo A. Wang, Hong-Wei Rappsilber, Juri Hochstrasser, Mark Cell Article Most short-lived eukaryotic proteins are degraded by the proteasome. A proteolytic core particle (CP) capped by regulatory particles (RPs) constitutes the 26S proteasome complex. RP biogenesis culminates with the joining of two large subcomplexes, the lid and base. In yeast and mammals, the lid appears to assemble completely before attaching to the base, but how this hierarchical assembly is enforced has remained unclear. Using biochemical reconstitutions, quantitative cross-linking/mass spectrometry, and electron microscopy, we resolve the mechanistic basis for the linkage between lid biogenesis and lid-base joining. Assimilation of the final lid subunit, Rpn12, triggers a large-scale conformational remodeling of the nascent lid that drives RP assembly, in part by relieving steric clash with the base. Surprisingly, this remodeling is triggered by a single Rpn12 α helix. Such assembly-coupled conformational switching is reminiscent of viral particle maturation and may represent a commonly used mechanism to enforce hierarchical assembly in multisubunit complexes. Cell Press 2015-10-08 /pmc/articles/PMC4601081/ /pubmed/26451487 http://dx.doi.org/10.1016/j.cell.2015.09.022 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Tomko, Robert J. Taylor, David W. Chen, Zhuo A. Wang, Hong-Wei Rappsilber, Juri Hochstrasser, Mark A Single α Helix Drives Extensive Remodeling of the Proteasome Lid and Completion of Regulatory Particle Assembly |
title | A Single α Helix Drives Extensive Remodeling of the Proteasome Lid and Completion of Regulatory Particle Assembly |
title_full | A Single α Helix Drives Extensive Remodeling of the Proteasome Lid and Completion of Regulatory Particle Assembly |
title_fullStr | A Single α Helix Drives Extensive Remodeling of the Proteasome Lid and Completion of Regulatory Particle Assembly |
title_full_unstemmed | A Single α Helix Drives Extensive Remodeling of the Proteasome Lid and Completion of Regulatory Particle Assembly |
title_short | A Single α Helix Drives Extensive Remodeling of the Proteasome Lid and Completion of Regulatory Particle Assembly |
title_sort | single α helix drives extensive remodeling of the proteasome lid and completion of regulatory particle assembly |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601081/ https://www.ncbi.nlm.nih.gov/pubmed/26451487 http://dx.doi.org/10.1016/j.cell.2015.09.022 |
work_keys_str_mv | AT tomkorobertj asingleahelixdrivesextensiveremodelingoftheproteasomelidandcompletionofregulatoryparticleassembly AT taylordavidw asingleahelixdrivesextensiveremodelingoftheproteasomelidandcompletionofregulatoryparticleassembly AT chenzhuoa asingleahelixdrivesextensiveremodelingoftheproteasomelidandcompletionofregulatoryparticleassembly AT wanghongwei asingleahelixdrivesextensiveremodelingoftheproteasomelidandcompletionofregulatoryparticleassembly AT rappsilberjuri asingleahelixdrivesextensiveremodelingoftheproteasomelidandcompletionofregulatoryparticleassembly AT hochstrassermark asingleahelixdrivesextensiveremodelingoftheproteasomelidandcompletionofregulatoryparticleassembly AT tomkorobertj singleahelixdrivesextensiveremodelingoftheproteasomelidandcompletionofregulatoryparticleassembly AT taylordavidw singleahelixdrivesextensiveremodelingoftheproteasomelidandcompletionofregulatoryparticleassembly AT chenzhuoa singleahelixdrivesextensiveremodelingoftheproteasomelidandcompletionofregulatoryparticleassembly AT wanghongwei singleahelixdrivesextensiveremodelingoftheproteasomelidandcompletionofregulatoryparticleassembly AT rappsilberjuri singleahelixdrivesextensiveremodelingoftheproteasomelidandcompletionofregulatoryparticleassembly AT hochstrassermark singleahelixdrivesextensiveremodelingoftheproteasomelidandcompletionofregulatoryparticleassembly |