Nucleotide-dependent switch in proteasome assembly mediated by the Nas6 chaperone

作者：Li Frances; Tian Geng; Langager Deanna; Sokolova Vladyslava; Finley Daniel; Park Soyeon^*

来源：Proceedings of the National Academy of Sciences of the United States of America, 2017, 114(7): 1548-1553.

DOI：10.1073/pnas.1612922114

• proteasome
• chaperone
• AAA(+) ATPase
• assembly
• Nas6

The 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.

• 出版日期2017-2-14