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Journal Articles Biophysical Chemistry Year : 2024

Magnetic resonance investigation of conformational responses of tau protein to specific phosphorylation

Abstract

Intrinsically disordered proteins (IDPs) are known to adopt many rapidly interconverting structures, making it difficult to pinpoint the specific conformational states that are relevant for their function. Tau is an important IDP, and its conformation is known to be affected by post-translational modifications (PTMs), such as phosphorylation. To investigate the effect of specific phosphorylation on full-length Tau's dynamic global conformation, we employed a combination of nuclear magnetic resonance-based paramagnetic relaxation interference methods and electron paramagnetic resonance spectroscopy. By reproducing the AT8 epitope, comprising exclusive phosphorylation at residues S202 and T205, we were able to identify conformations specific to phosphorylated Tau, which exhibited a tendency towards less compact states. These mechanistic details are of significance to understand the path leading from soluble Tau to the ordered structure of Tau fibers. This approach proved to be successful for studying the conformational changes of (phosphorylated) full-length Tau and can potentially be extended to the study of other IDPs that undergo various PTMs.
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Thursday, February 6, 2025
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Thursday, February 6, 2025
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hal-04440623 , version 1 (06-02-2024)

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Alessia Lasorsa, Hamida Merzougui, François-Xavier Cantrelle, Giuseppe Sicoli, Elian Dupré, et al.. Magnetic resonance investigation of conformational responses of tau protein to specific phosphorylation. Biophysical Chemistry, 2024, Part of special issue Biophysical, Biochemical, and Cellular Events Underlying Proteinopathies Edited by Carmelo La Rosa, Danilo Milardi, Magdalena Ivanova, Andisheh Abedini, Lucie Khemtemourian, Ayyalusamy Ramamoorthy, 305 (107155), pp.107155. ⟨10.1016/j.bpc.2023.107155⟩. ⟨hal-04440623⟩
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