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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...

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Autores principales: Tomko, Robert J., Taylor, David W., Chen, Zhuo A., Wang, Hong-Wei, Rappsilber, Juri, Hochstrasser, Mark
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
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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.
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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
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