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Reconfiguration of the proteasome during chaperone-mediated assembly

The proteasomal ATPase ring, comprising Rpt1-Rpt6, associates with the heptameric α ring of the proteasome core particle (CP) in the mature proteasome, with the Rpt C-terminal tails inserting into pockets of the α ring(1–4). Rpt ring assembly is mediated by four chaperones, each binding a distinct R...

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Detalles Bibliográficos
Autores principales: Park, Soyeon, Li, Xueming, Kim, Ho Min, Singh, Chingakham Ranjit, Tian, Geng, Hoyt, Martin A., Lovell, Scott, Battaile, Kevin P., Zolkiewski, Michal, Coffino, Philip, Roelofs, Jeroen, Cheng, Yifan, Finley, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3687086/
https://www.ncbi.nlm.nih.gov/pubmed/23644457
http://dx.doi.org/10.1038/nature12123
Descripción
Sumario:The proteasomal ATPase ring, comprising Rpt1-Rpt6, associates with the heptameric α ring of the proteasome core particle (CP) in the mature proteasome, with the Rpt C-terminal tails inserting into pockets of the α ring(1–4). Rpt ring assembly is mediated by four chaperones, each binding a distinct Rpt subunit(5–10). We report that the base subassembly of the proteasome, which includes the Rpt ring, forms a high affinity complex with the CP. This complex is subject to active dissociation by the chaperones Hsm3, Nas6, and Rpn14. Chaperone-mediated dissociation was abrogated by a nonhydrolyzable ATP analog, indicating that chaperone action is coupled to nucleotide hydrolysis by the Rpt ring. Unexpectedly, synthetic Rpt tail peptides bound α pockets with poor specificity, except for Rpt6, which uniquely bound the α2/α3 pocket. Although the Rpt6 tail is not visualized within an α pocket in mature proteasomes(2–4), it inserts into the α2/α3 pocket in the base-CP complex and is important for complex formation. Thus, the Rpt-CP interface is reconfigured when the lid complex joins the nascent proteasome to form the mature holoenzyme.