9C21

Structure of endogenous Actin filament from rat model of Alzheimer's disease

Summary for 9C21

• Entry DOI: 10.2210/pdb9c21/pdb
• EMDB information: 45135
• Descriptor: Actin, cytoplasmic 1 (1 entity in total)
• Functional Keywords: contractile protein, cytoskeletal, structural protein
• Biological source: Rattus norvegicus (Norway rat)
• Total number of polymer chains: 6
• Total formula weight: 250774.08

Authors

Khalili Samani, E.,Keszei, A.F.A.,Mazhab-Jafari, M.T. (deposition date: 2024-05-30, release date: 2024-12-11, Last modification date: 2025-01-15)

Primary citation

Samani, E.K.,Hasan, S.M.N.,Waas, M.,Keszei, A.F.A.,Xu, X.,Heydari, M.,Hill, M.E.,McLaurin, J.,Kislinger, T.,Mazhab-Jafari, M.T.
Unveiling the structural proteome of an Alzheimer's disease rat brain model.
Structure, 33:51-, 2025

PubMed Abstract: 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.

PubMed: 39615488
DOI: 10.1016/j.str.2024.11.004

Experimental method

ELECTRON MICROSCOPY (3.4 Å)