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TitleUnveiling the structural proteome of an Alzheimer's disease rat brain model.
Journal, issue, pagesStructure, Vol. 33, Issue 1, Page 51-61.e3, Year 2025
Publish dateNov 21, 2024
AuthorsElnaz 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 AbstractStudying 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.
External linksStructure / PubMed:39615488
MethodsEM (helical sym.) / EM (single particle)
Resolution2.73 - 4.24 Å
Structure data

45135

9c21

EMDB-45135, PDB-9c21:
Structure of endogenous Actin filament from rat model of Alzheimer's disease
Method: EM (helical sym.) / Resolution: 3.4 Å

45137

9c28

EMDB-45137: Structure of endogenous Actin filament from rat model of Alzheimer's disease
PDB-9c28: Structure of endogenous Glutamine synthetase from rat model of Alzheimer's disease
Method: EM (single particle) / Resolution: 3.12 Å

45183

9c4e

EMDB-45183, PDB-9c4e:
Structure of endogenous DPYSL2 from rat model of Alzheimer's disease
Method: EM (single particle) / Resolution: 2.73 Å

45298

9c86

EMDB-45298, PDB-9c86:
Structure of endogenous asymmetric DPYSL2 from rat model of Alzheimer's disease
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-47474: cryoEM map of endogenous V1 region of V-ATPase from rat model of Alzheimer's disease
Method: EM (single particle) / Resolution: 4.24 Å

Chemicals

ChemComp-MN:
Unknown entry

ChemComp-GLY:
GLYCINE

Source
  • rattus norvegicus (Norway rat)
KeywordsSTRUCTURAL PROTEIN / Contractile protein / cytoskeletal / LIGASE / Glutamine synthetase / NEUROPEPTIDE / Dihydropyrimidinase-related protein 2

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