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-Structure paper
| タイトル | How Sup35 monomer conformation and amyloid fibril polymorphism determine yeast strain phenotypes. |
|---|---|
| ジャーナル・号・ページ | Res Sq, Year 2025 |
| 掲載日 | 2025年11月3日 |
著者 | Motomasa Tanaka / Takashi Nomura / David Boyer / Yusuke Komi / Peng Ge / Rodrigo A Maillard / Piere Rodriguez / Atsushi Yamagata / Mikako Shirouzu / Giuseppe Legname / Bruno Samori / David Eisenberg / ![]() |
| PubMed 要旨 | In the [ ] prion system, the yeast prion protein Sup35 can form structurally distinct amyloid fibrils that lead to distinct transmissible prion states, or strains. However, our understanding of how ...In the [ ] prion system, the yeast prion protein Sup35 can form structurally distinct amyloid fibrils that lead to distinct transmissible prion states, or strains. However, our understanding of how different Sup35 fibril structures arise and translate to phenotypic variations is limited. Here, using cryo-EM and single-monomer force spectroscopy with optical tweezers, we reveal the structural basis of yeast prion propagation in four wild-type and S17R mutant variants of Sup35 that underlie different [ ] strains. Cryo-EM structures show that the four variants form strikingly distinct fibril structures, which exhibit varying stability and chaperone-accessibility. Force spectroscopy suggests the different distinct fibril structures are derived from distinct monomer conformational ensembles. Further, cryo-EM structures indicate that prion strain strength is correlated with enhanced fibril propagation caused by a combination of low fibril stability and a large separation between the Sup35 fibril core and the Ssa1/Sis1 chaperone-binding region. These results provide a structure-based mechanism for the yeast prion strain phenomenon with implications for understanding amyloid propagation in human neurodegenerative diseases. |
リンク | Res Sq / PubMed:41282265 / PubMed Central |
| 手法 | EM (らせん対称) |
| 解像度 | 2.2 - 3.1 Å |
| 構造データ | EMDB-66703, PDB-9xbk: EMDB-66704, PDB-9xbl: EMDB-66705, PDB-9xbm: EMDB-66706, PDB-9xbn: EMDB-66707, PDB-9xbo: EMDB-66708, PDB-9xbp: |
| 化合物 | ![]() ChemComp-HOH: |
| 由来 |
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キーワード | PROTEIN FIBRIL / Yeast / Sup35NM / Amyloid |
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