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-Structure paper
| タイトル | Structure of Blm10:13S proteasome intermediate reveals parallel assembly pathways for the proteasome core particle. |
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| ジャーナル・号・ページ | bioRxiv, Year 2024 |
| 掲載日 | 2024年11月5日 |
著者 | Mandeep Kaur / Xiang Chen / Stella Y Lee / Tyler M Weaver / Bret D Freudenthal / Kylie J Walters / Jeroen Roelofs / ![]() |
| PubMed 要旨 | Proteasomes are formed by chaperone-assisted assembly of core particles (CPs) and regulatory particles (RPs). The CP chaperone dimer Pba1/Pba2 binds early to proteasome subunits, and is thought to be ...Proteasomes are formed by chaperone-assisted assembly of core particles (CPs) and regulatory particles (RPs). The CP chaperone dimer Pba1/Pba2 binds early to proteasome subunits, and is thought to be replaced by Blm10 to form Blm10:CP, which promotes ATP-independent degradation of disordered proteins. Here, we present evidence of distinct parallel assembly pathways for CP by solving five cryo-EM structures including a Blm10:13S pre-assembly intermediate. Our data conflict with the current model of Blm10 and Pba1/Pba2 sequential activity in a single assembly pathway, as we find their CP binding is mutually exclusive and both are present on early and late assembly intermediates. CP affinity for Pba1/Pba2 is reduced during maturation, promoting Pba1/Pba2 release. We find Blm10 undergoes no such affinity switch, suggesting this pathway predominantly yields mature Blm10-bound CP. Altogether, our findings conflict with the current paradigm of sequential CP binding to instead indicate parallel assembly pathways by Pba1/Pba2 and Blm10. |
リンク | bioRxiv / PubMed:39574619 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.75 - 3.55 Å |
| 構造データ | EMDB-46461, PDB-9d0t: EMDB-46525, PDB-9d35: EMDB-46535, PDB-9d3i: EMDB-46559, PDB-9d4c: EMDB-46570, PDB-9d4u: |
| 由来 |
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キーワード | HYDROLASE / Proteasome / assembly chaperone / Blm10 / PA200 / Blm10-13S / Pba1 / CP / Cryo-EM / Assembly |
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