9c21
Structure of endogenous Actin filament from rat model of Alzheimer's disease
Structural highlights
FunctionACTB_RAT Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm of cells. Actin exists in both monomeric (G-actin) and polymeric (F-actin) forms, both forms playing key functions, such as cell motility and contraction. In addition to their role in the cytoplasmic cytoskeleton, G- and F-actin also localize in the nucleus, and regulate gene transcription and motility and repair of damaged DNA. Part of the ACTR1A/ACTB filament around which the dynactin complex is built. The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity).[UniProtKB:P60709][UniProtKB:Q6QAQ1] Publication Abstract from PubMedStudying 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. Unveiling the structural proteome of an Alzheimer's disease rat brain model.,Samani EK, Hasan SMN, Waas M, Keszei AFA, Xu X, Heydari M, Hill ME, McLaurin J, Kislinger T, Mazhab-Jafari MT Structure. 2024 Nov 29:S0969-2126(24)00494-5. doi: 10.1016/j.str.2024.11.004. PMID:39615488[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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