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-Structure paper
タイトル | Microgravity-Assisted Exploration of the Conformational Space of Amyloid β Affected by Tottori-Type Familial Mutation D7N. |
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ジャーナル・号・ページ | ACS Chem Neurosci, Year 2025 |
掲載日 | 2025年6月24日 |
![]() | Maho Yagi-Utsumi / Saeko Yanaka / Raymond N Burton-Smith / Chihong Song / Christian Ganser / Chiaki Yamazaki / Haruo Kasahara / Toru Shimazu / Takayuki Uchihashi / Kazuyoshi Murata / Koichi Kato / ![]() |
PubMed 要旨 | The amyloid β (Aβ) Tottori variant (D7N) exhibits unique aggregation behaviors and altered fibril formation, posing challenges for structural characterization. To overcome this, the microgravity ...The amyloid β (Aβ) Tottori variant (D7N) exhibits unique aggregation behaviors and altered fibril formation, posing challenges for structural characterization. To overcome this, the microgravity environment on the International Space Station was employed to study Tottori-type Aβ40 fibril formation and structure. Under Earth gravity, Tottori-type Aβ40 primarily formed nonfibrillar aggregates, hindering detailed structural analysis. In contrast, microgravity significantly enhanced fibril formation and minimized amorphous aggregates. Cryo-electron microscopy revealed two structurally distinct fibril types, each comprising different protomer conformations. In both types, the N-terminal segment was disordered and nor resolved in the density maps. The D7N mutation disrupts the protection of the core by the N-terminal segment often observed in wild-type Aβ40 fibrils, enhancing the hydrophobicity-mediated aggregation propensity. However, microgravity suppressed kinetic traps and facilitated high-quality fibril formation suitable for structural studies that can explore the free energy landscape of Aβ fibril formation. These findings demonstrate the utility of microgravity for studying familial Aβ variants and potentially accelerate our understanding of Aβ aggregation mechanisms in Alzheimer's disease. |
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手法 | EM (らせん対称) |
解像度 | 3.1 - 3.6 Å |
構造データ | EMDB-63646: I-shaped amyloid fiber (40) of Tottori (D7N) mutant EMDB-63647: V-shaped amyloid fiber (40) of Tottori (D7N) mutant (type 1) EMDB-63648: V'-shaped short pitch amyloid fiber (40) of Tottori (D7N) mutant EMDB-64274: V-shaped amyloid fiber (40) of Tottori (D7N) mutant (type 2) |
由来 |
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![]() | PROTEIN FIBRIL / Amyloid |