The 26S proteasome is the central ATP-dependent protease in eukaryotes and is essential for organismal health. Proteasome assembly is mediated by several dedicated, evolutionarily conserved chaperone proteins. These chaperones associate transiently with assembly intermediates but are absent from mature proteasomes. Chaperone eviction upon completion of proteasome assembly is necessary for normal proteasome function, but how they are released remains unresolved. Here, we demonstrate that the Nas6 assembly chaperone, homolog of the human oncogene gankyrin, is evicted from nascent proteasomes during completion of assembly via a conformation-specific allosteric interaction of the Rpn5 subunit with the proteasomal ATPase ring. Subsequent ATP binding by the ATPase subunit Rpt3 promotes conformational remodeling of the ATPase ring that evicts Nas6 from the nascent proteasome. Our study demonstrates how assembly-coupled allosteric signals promote chaperone eviction and provides a framework for understanding the eviction of other chaperones from this biomedically important molecular machine.
Pubmed ID: 30625330 RIS Download
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A software tool for profiling Short Tandem Repeats (STRs) from high throughput sequencing data.
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View all literature mentionsThis monoclonal targets Ubiquitin
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View all literature mentionsThis polyclonal targets Proteasome 19S Rpt5/S6a subunit pAb
View all literature mentionsThis monoclonal targets slightly modified β-cytoplasmic actin N-terminal peptide, Ac-Asp-Asp-Asp-Ile-Ala-Ala-Leu-Val-Ile-Asp-Asn-Gly-Ser-Gly-Lys, conjugated to KLH
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis unknown targets Proteasome 20S core subunits pAb
View all literature mentionsThis polyclonal targets Proteasome 19S Rpt5/S6a subunit pAb
View all literature mentionsThis monoclonal targets Ubiquitin
View all literature mentionsThis unknown targets Glucose-6-Phosphate Dehydrogenase (G-6-PDH)
View all literature mentions