Li, FrancesTian, GengLangager, DeannaSokolova, VladyslavaFinley, DanielPark, Soyeon2019-10-052017Li, Frances, Geng Tian, Deanna Langager, Vladyslava Sokolova, Daniel Finley, and Soyeon Park. 2017. “Nucleotide-Dependent Switch in Proteasome Assembly Mediated by the Nas6 Chaperone.” Proceedings of the National Academy of Sciences 114 (7): 1548–53. https://doi.org/10.1073/pnas.1612922114.0027-84240744-28311091-6490http://nrs.harvard.edu/urn-3:HUL.InstRepos:41483215The proteasome is assembled via the nine-subunit lid, nine-subunit base, and 28-subunit core particle (CP). Previous work has shown that the chaperones Rpn14, Nas6, Hsm3, and Nas2 each bind a specific ATPase subunit of the base and antagonize base-CP interaction. Here, we show that the Nas6 chaperone also obstructs base-lid association. Nas6 alternates between these two inhibitory modes according to the nucleotide state of the base. When ATP cannot be hydrolyzed, Nas6 interferes with base-lid, but not base-CP, association. In contrast, under conditions of ATP hydrolysis, Nas6 obstructs base-CP, but not base-lid, association. Modeling of Nas6 into cryoelectron microscopy structures of the proteasome suggests that Nas6 controls both base-lid affinity and base-CP affinity through steric hindrance; Nas6 clashes with the lid in the ATP-hydrolysis-blocked proteasome, but clashes instead with the CP in the ATP-hydrolysis-competent proteasome. Thus, Nas6 provides a dual mechanism to control assembly at both major interfaces of the proteasome.en-USJournal Article2019-10-0510.1073/pnas.1612922114