Informace o publikaci
The effect of phosphoserine 324 on the paired helical filaments of tau protein
| Název česky | Vliv fosfoserinu 324 na párové helikální filamenty tau proteinu |
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| Autoři | |
| Rok publikování | 2024 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | Intrinsically disordered tau protein belongs to the family of microtubule-associated proteins whose primary function is the stabilization and regulation of the microtubules. The properties and function of tau are heavily dependent on its post-translational modifications, including phosphorylation, glycosylation, acetylation, truncation, and others [1]. Especially phosphorylation and truncation are closely associated with tau protein aggregation, which is a common tau pathology present in Alzheimer’s disease and other neurodegenerative diseases. Each of them is characterized by a specific type of tau fibrils. Neurofibrillary tangles composed of paired helical filaments and straight filaments are typical for Alzheimer’s disease [2]. The study of the tau aggregation mechanism experimentally is still a challenging task. Molecular dynamics simulations provide us with a helpful insight into the dynamics of the fibrils [3,4]. It has already been published that certain phosphorylations can enhance the stability of the paired helical filaments of tau protein [5]. In our study, we explore the effect of the phosphorylated Ser324 on the free energy profile of the dissociation of the paired helical filaments. This phosphorylation position is highly relevant for Alzheimer’s disease because it is frequently present in the neurofibrillary tangles. [1] Ye, Haiqiong, et al. "The role of post-translational modifications on the structure and function of tau protein." Journal of Molecular Neuroscience 72.8 (2022): 1557-1571. [2] Fitzpatrick, Anthony WP, et al. "Cryo-EM structures of tau filaments from Alzheimer’s disease." Nature 547.7662 (2017): 185-190. [3] Liu, Hongli, et al. "Disclosing the template-induced misfolding mechanism of tau protein by studying the dissociation of the boundary chain from the formed tau fibril based on a steered molecular dynamics simulation." ACS Chemical Neuroscience 10.3 (2019): 1854-1865. [4] Zapletal, Vojtěch, et al. "Choice of force field for proteins containing structured and intrinsically disordered regions." Biophysical journal 118.7 (2020): 1621-1633. [5] Leonard, Cass, Christian Phillips, and James McCarty. "Insight into seeded tau fibril growth from molecular dynamics simulation of the Alzheimer’s disease protofibril core." Frontiers in molecular biosciences 8 (2021): 624302. |
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