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-Structure paper
| タイトル | Unveiling the structural proteome of an Alzheimer's disease rat brain model. |
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| ジャーナル・号・ページ | Structure, Vol. 33, Issue 1, Page 51-61.e3, Year 2025 |
| 掲載日 | 2025年1月2日 |
著者 | Elnaz Khalili Samani / S M Naimul Hasan / Matthew Waas / Alexander F A Keszei / Xiaoxiao Xu / Mahtab Heydari / Mary Elizabeth Hill / JoAnne McLaurin / Thomas Kislinger / Mohammad T Mazhab-Jafari / ![]() |
| PubMed 要旨 | Studying native protein structures at near-atomic resolution in a crowded environment presents challenges. Consequently, understanding the structural intricacies of proteins within pathologically ...Studying native protein structures at near-atomic resolution in a crowded environment presents challenges. Consequently, understanding the structural intricacies of proteins within pathologically affected tissues often relies on mass spectrometry and proteomic analysis. Here, we utilized cryoelectron microscopy (cryo-EM) and the Build and Retrieve (BaR) method to investigate protein complexes' structural characteristics such as post-translational modification, active site occupancy, and arrested conformational state in Alzheimer's disease (AD) using brain lysate from a rat model (TgF344-AD). Our findings reveal novel insights into the architecture of these complexes, corroborated through mass spectrometry analysis. Interestingly, it has been shown that the dysfunction of these protein complexes extends beyond AD, implicating them in cancer, as well as other neurodegenerative disorders such as Parkinson's disease, Huntington's disease, and schizophrenia. By elucidating these structural details, our work not only enhances our understanding of disease pathology but also suggests new avenues for future approaches in therapeutic intervention. |
リンク | Structure / PubMed:39615488 |
| 手法 | EM (らせん対称) / EM (単粒子) |
| 解像度 | 2.73 - 4.24 Å |
| 構造データ | EMDB-45135, PDB-9c21: EMDB-45137: Structure of endogenous Actin filament from rat model of Alzheimer's disease EMDB-45183, PDB-9c4e: EMDB-45298, PDB-9c86: ![]() EMDB-47474: cryoEM map of endogenous V1 region of V-ATPase from rat model of Alzheimer's disease |
| 化合物 | ![]() ChemComp-MN: ![]() ChemComp-GLY: |
| 由来 |
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キーワード | STRUCTURAL PROTEIN / Contractile protein / cytoskeletal / LIGASE / Glutamine synthetase / NEUROPEPTIDE / Dihydropyrimidinase-related protein 2 |
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