Nucleotide-dependent switch in proteasome assembly mediated by the Nas6 chaperone
| Autor: | Frances Li, Vladyslava Sokolova, Geng Tian, Deanna Langager, Soyeon Park, Daniel Finley |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Steric effects Models Molecular Proteasome Endopeptidase Complex Saccharomyces cerevisiae Proteins Protein subunit ATPase Saccharomyces cerevisiae 03 medical and health sciences Adenosine Triphosphate Protein Domains ATP hydrolysis Nucleotide chemistry.chemical_classification Multidisciplinary biology Nucleotides Hydrolysis Cryoelectron Microscopy Biological Sciences 030104 developmental biology chemistry Proteasome Biochemistry Chaperone (protein) Proteasome assembly biology.protein Biophysics Molecular Chaperones Protein Binding |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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