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

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.
Mesh Terms:
Adenosine Triphosphate, Cryoelectron Microscopy, Hydrolysis, Models, Molecular, Molecular Chaperones, Nucleotides, Proteasome Endopeptidase Complex, Protein Binding, Protein Domains, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
Proc. Natl. Acad. Sci. U.S.A.
Date: Dec. 14, 2016
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