Multistep Changes in Amyloid Structure Induced by Cross-Seeding on a Rugged Energy Landscape
| Autor: | Keisuke Yuzu, Masatomo So, Yuji Goto, Eri Chatani, Tetsushi Iwasaki, Naoki Yamamoto, Masahiro Noji, Motonari Tsubaki |
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| Rok vydání: | 2021 |
| Předmět: |
Amyloid
medicine.medical_treatment Biophysics Protein Structure Secondary 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Protein structure mental disorders medicine Animals Humans Insulin Protein secondary structure 030304 developmental biology 0303 health sciences Amyloidosis Energy landscape Articles medicine.disease Phenotype chemistry Cattle Thioflavin 030217 neurology & neurosurgery |
| Zdroj: | Biophys J |
| ISSN: | 0006-3495 |
| Popis: | Amyloid fibrils are aberrant protein aggregates associated with various amyloidoses and neurodegenerative diseases. It is recently indicated that structural diversity of amyloid fibrils often results in different pathological phenotypes, including cytotoxicity and infectivity. The diverse structures are predicted to propagate by seed-dependent growth, which is one of the characteristic properties of amyloid fibrils. However, much remains unknown regarding how exactly the amyloid structures are inherited to subsequent generations by seeding reaction. Here, we investigated the behaviors of self- and cross-seeding of amyloid fibrils of human and bovine insulin in terms of thioflavin T fluorescence, morphology, secondary structure, and iodine staining. Insulin amyloid fibrils exhibited different structures, depending on species, each of which replicated in self-seeding. In contrast, gradual structural changes were observed in cross-seeding, and a new type of amyloid structure with distinct morphology and cytotoxicity was formed when human insulin was seeded with bovine insulin seeds. Remarkably, iodine staining tracked changes in amyloid structure sensitively, and singular value decomposition analysis of the ultraviolet-visible absorption spectra of the fibril-bound iodine has revealed the presence of one or more intermediate metastable states during the structural changes. From these findings, we propose a propagation scheme with multistep structural changes in cross-seeding between two heterologous proteins, which is accounted for as a consequence of the rugged energy landscape of amyloid formation. |
| Databáze: | OpenAIRE |
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