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-Structure paper
タイトル | Structure of the preholoproteasome reveals late steps in proteasome core particle biogenesis. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 30, Issue 10, Page 1516-1524, Year 2023 |
掲載日 | 2023年8月31日 |
著者 | Richard M Walsh / Shaun Rawson / Helena M Schnell / Benjamin Velez / Tamayanthi Rajakumar / John Hanna / |
PubMed 要旨 | Assembly of the proteasome's core particle (CP), a barrel-shaped chamber of four stacked rings, requires five chaperones and five subunit propeptides. Fusion of two half-CP precursors yields a ...Assembly of the proteasome's core particle (CP), a barrel-shaped chamber of four stacked rings, requires five chaperones and five subunit propeptides. Fusion of two half-CP precursors yields a complete structure but remains immature until active site maturation. Here, using Saccharomyces cerevisiae, we report a high-resolution cryogenic electron microscopy structure of preholoproteasome, a post-fusion assembly intermediate. Our data reveal how CP midline-spanning interactions induce local changes in structure, facilitating maturation. Unexpectedly, we find that cleavage may not be sufficient for propeptide release, as residual interactions with chaperones such as Ump1 hold them in place. We evaluated previous models proposing that dynamic conformational changes in chaperones drive CP fusion and autocatalytic activation by comparing preholoproteasome to pre-fusion intermediates. Instead, the data suggest a scaffolding role for the chaperones Ump1 and Pba1/Pba2. Our data clarify key aspects of CP assembly, suggest that undiscovered mechanisms exist to explain CP fusion/activation, and have relevance for diseases of defective CP biogenesis. |
リンク | Nat Struct Mol Biol / PubMed:37653242 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.4 - 3.0 Å |
構造データ | EMDB-40938, PDB-8t08: EMDB-40944, PDB-8t0m: |
由来 |
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キーワード | HYDROLASE / Preholo-proteasome / core particle / Proteasome |