| Autor: |
Gea Cereghetti, Vera Maria Kissling, Lisa Maria Koch, Alexandra Arm, Pavel Afanasyev, Miriam Linsenmeier, Cédric Eichmann, Jiangtao Zhou, Yiping Cao, Dorota Maria Pfizenmaier, Sonja Kroschwald, Thomas Wiegand, Riccardo Cadalbert, Daniel Böhringer, Raffaele Mezzenga, Paolo Arosio, Roland Riek, Matthias Peter |
| Rok vydání: |
2022 |
| DOI: |
10.1101/2022.03.21.484600 |
| Popis: |
Amyloids were long viewed as irreversible, pathological aggregates, often associated with neurodegenerative diseases1. However, recent insights challenge this view, providing evidence that reversible amyloids can form upon stress conditions and fulfil crucial cellular functions2. Yet, the molecular mechanisms regulating functional amyloids and the differences to their pathological counterparts remain poorly understood. Here we investigate the conserved principles of amyloid reversibility by studying the essential metabolic enzyme pyruvate kinase (PK) in yeast and human cells. We demonstrate that PK forms stress-dependent reversible amyloids through a pH-sensitive amyloid core. Stress- induced cytosolic acidification promotes aggregate formation via protonation of specific glutamate (in yeast) or histidine (in human) residues within the amyloid core. Our work thus unravels a conserved and potentially widespread mechanism underlying amyloid functionality and reversibility, fine-tuned to the respective physiological cellular pH range. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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