Analysis of the effect of environmental factors on the structure of catalytic amyloid fibrils
Final Report Abstract
Amyloid fibrils are filamentous polypeptide aggregates of great scientific relevance due to their association with diseases including Alzheimer’s, Parkinson’s and systemic amyloidosis. While the abnormal formation of these misfolded states inside the human body can lead to severe health problems, there are increasing attempts to utilize amyloid structures due to their unique structural and chemical properties for biotechnological purposes. The aim of this project was to use catalytic amyloid as a model system to determine the effect of environmental factors on the polymorphic structure and catalytic efficiency of amyloids. To that end, we combined methods of structural biology, in particular cryo-electron microscopy, with mathematical approaches to statistically assess fibril samples at a single particle level and to generally improve their structural analysis. Our data produced a new model of the catalytic center of the fibrils and explain why the catalytic efficiency is dependent of the aggregate morphology. The mathematical data analysis was based on AI-techniques, in particular neural networks, and on further methods of digital image analysis for the pre- and post-processing of image data measured by cryo-electron microscopy, where the processed data were then modelled by multivariate probability distributions.
Publications
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Automatic identification of crossovers in cryo‐EM images of murine amyloid protein A fibrils with machine learning. Journal of Microscopy, 277(1), 12-22.
WEBER, MATTHIAS; BÄUERLE, ALEX; SCHMIDT, MATTHIAS; NEUMANN, MATTHIAS; FÄNDRICH, MARCUS; ROPINSKI, TIMO & SCHMIDT, VOLKER
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AA amyloid fibrils from diseased tissue are structurally different from in vitro formed SAA fibrils. Nature Communications, 12(1).
Bansal, Akanksha; Schmidt, Matthias; Rennegarbe, Matthies; Haupt, Christian; Liberta, Falk; Stecher, Sabrina; Puscalau-Girtu, Ioana; Biedermann, Alexander & Fändrich, Marcus
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Role of mutations and post-translational modifications in systemic AL amyloidosis studied by cryo-EM. Nature Communications, 12(1).
Radamaker, Lynn; Karimi-Farsijani, Sara; Andreotti, Giada; Baur, Julian; Neumann, Matthias; Schreiner, Sarah; Berghaus, Natalie; Motika, Raoul; Haupt, Christian; Walther, Paul; Schmidt, Volker; Huhn, Stefanie; Hegenbart, Ute; Schönland, Stefan O.; Wiese, Sebastian; Read, Clarissa; Schmidt, Matthias & Fändrich, Marcus
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Cryo-EM structure of a catalytic amyloid fibril. Scientific Reports, 13(1).
Heerde, Thomas; Bansal, Akanksha; Schmidt, Matthias & Fändrich, Marcus
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Segmentation and morphological analysis of amyloid fibrils from cryo-EM image data. Journal of Mathematics in Industry, 13(1).
Weber, Matthias; Neumann, Matthias; Schmidt, Matthias; Pfeiffer, Peter Benedikt; Bansal, Akanksha; Fändrich, Marcus & Schmidt, Volker
