Expanded Conformations of Monomeric Tau Initiate Its Amyloidogenesis
| العنوان: | Expanded Conformations of Monomeric Tau Initiate Its Amyloidogenesis |
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| المؤلفون: | María del Carmen Fernández‐Ramírez, Kevin Kan‐Shing Ng, Margarita Menéndez, Douglas V. Laurents, Rubén Hervás, Mariano Carrión‐Vázquez |
| المساهمون: | Agencia Estatal de Investigación (España), Consejo Superior de Investigaciones Científicas (España) |
| المصدر: | Angewandte Chemie (International ed. in English). |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Aggregation, Amyloid Polymorphism, Tauopathies, Single-Molecule Studies, General Chemistry, General Medicine, Tau, Catalysis |
| الوصف: | 11 pags., 5 figs. Understanding early amyloidogenesis is key to rationally develop therapeutic strategies. Tau protein forms well-characterized pathological deposits but its aggregation mechanism is still poorly understood. Using single-molecule force spectroscopy based on a mechanical protection strategy, we studied the conformational landscape of the monomeric tau repeat domain (tauRD244-368). We found two sets of conformational states, whose frequency is influenced by mutations and the chemical context. While pathological mutations Δ280K and P301L and a pro-amyloidogenic milieu favored expanded conformations and destabilized local structures, an anti-amyloidogenic environment promoted a compact ensemble, including a conformer whose topology might mask two amyloidogenic segments. Our results reveal that to initiate aggregation, monomeric tau-RD244-368 decreases its polymorphism adopting expanded conformations. This could account for the distinct structures found in vitro and across tauopathies. Spanish Agency for Research (AEI). Grant Numbers: SAF2016-76678-C2-1-R, SAF2016-76678-C2-2-R, BFU2015-70072-R |
| تدمد: | 1521-3773 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3ec41f38ddd764f706719f308e941755 https://pubmed.ncbi.nlm.nih.gov/36542681 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3ec41f38ddd764f706719f308e941755 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15213773 |
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