Cryo-EM demonstrates the in vitro proliferation of an ex vivo amyloid fibril morphology by seeding
| العنوان: | Cryo-EM demonstrates the in vitro proliferation of an ex vivo amyloid fibril morphology by seeding |
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| المؤلفون: | Thomas Heerde, Matthies Rennegarbe, Alexander Biedermann, Dilan Savran, Peter B. Pfeiffer, Manuel Hitzenberger, Julian Baur, Ioana Puscalau-Girtu, Martin Zacharias, Nadine Schwierz, Christian Haupt, Matthias Schmidt, Marcus Fändrich |
| المصدر: | Nature Communications Nature Communications, Vol 13, Iss 1, Pp 1-8 (2022) |
| بيانات النشر: | Nature Publishing Group UK, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | DDC 540 / Chemistry & allied sciences, Amyloid, Prions, Protein Conformation, Science, Genetic Vectors, General Physics and Astronomy, Gene Expression, Mice, Transgenic, macromolecular substances, Molecular Dynamics Simulation, General Biochemistry, Genetics and Molecular Biology, Article, Mice, DDC 570 / Life sciences, Cryoelectron microscopy, ddc:570, Escherichia coli, Animals, Humans, Protein Isoforms, ddc:530, Cloning, Molecular, Serum Amyloid A Protein, Multidisciplinary, Protein Stability, Cryoelectron Microscopy, food and beverages, General Chemistry, Amyloidosis, Molecular conformation, Recombinant Proteins, ddc:540, Proteolysis, Prion, Protein aggregation, Endopeptidase K |
| الوصف: | Several studies showed that seeding of solutions of monomeric fibril proteins with ex vivo amyloid fibrils accelerated the kinetics of fibril formation in vitro but did not necessarily replicate the seed structure. In this research we use cryo-electron microscopy and other methods to analyze the ability of serum amyloid A (SAA)1.1-derived amyloid fibrils, purified from systemic AA amyloidosis tissue, to seed solutions of recombinant SAA1.1 protein. We show that 98% of the seeded fibrils remodel the full fibril structure of the main ex vivo fibril morphology, which we used for seeding, while they are notably different from unseeded in vitro fibrils. The seeded fibrils show a similar proteinase K resistance as ex vivo fibrils and are substantially more stable to proteolytic digestion than unseeded in vitro fibrils. Our data support the view that the fibril morphology contributes to determining proteolytic stability and that pathogenic amyloid fibrils arise from proteolytic selection. publishedVersion |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::29953e768386712fcd255c923e97f72fTest http://europepmc.org/articles/PMC8748726Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....29953e768386712fcd255c923e97f72f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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