Proteasome Activation is Mediated via a Functional Switch of the Rpt6 C-terminal Tail Following Chaperone-dependent Assembly
| Autor: | Frances Li, Vladyslava Sokolova, Soyeon Park, George Polovin |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular Proteasome Endopeptidase Complex Saccharomyces cerevisiae Proteins ATPase Immunoblotting Saccharomyces cerevisiae Plasma protein binding Article Protein structure Binding site Adenosine Triphosphatases Binding Sites Multidisciplinary biology Temperature biology.organism_classification Ubiquitinated Proteins Protein Structure Tertiary Cell biology Biochemistry Proteasome Proteasome assembly Chaperone (protein) Mutation biology.protein Molecular Chaperones Protein Binding |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep14909 |
| Popis: | In the proteasome, the proteolytic 20S core particle (CP) associates with the 19S regulatory particle (RP) to degrade polyubiquitinated proteins. Six ATPases (Rpt1-Rpt6) of the RP form a hexameric Rpt ring and interact with the heptameric α ring (α1–α7) of the CP via the Rpt C-terminal tails individually binding to the α subunits. Importantly, the Rpt6 tail has been suggested to be crucial for RP assembly. Here, we show that the interaction of the CP and Rpt6 tail promotes a CP-Rpt3 tail interaction and that they jointly mediate proteasome activation via opening the CP gate for substrate entry. The Rpt6 tail forms a novel relationship with the Nas6 chaperone, which binds to Rpt3 and regulates the CP-Rpt3 tail interaction, critically influencing cell growth and turnover of polyubiquitinated proteins. CP-Rpt6 tail binding promotes the release of Nas6 from the proteasome. Based on disulfide crosslinking that detects cognate α3-Rpt6 tail and α2-Rpt3 tail interactions in the proteasome, decreased α3-Rpt6 tail interaction facilitates robust α2-Rpt3 tail interaction that is also strongly ATP-dependent. Together, our data support the reported role of Rpt6 during proteasome assembly and suggest that its function switches from anchoring for RP assembly into promoting Rpt3-dependent activation of the mature proteasome. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|